To see the other types of publications on this topic, follow the link: Brown Adipocytes.
Journal articles on the topic 'Brown Adipocytes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Brown Adipocytes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Okamatsu-Ogura, Yuko, Junko Nio-Kobayashi, Kazuki Nagaya, Ayumi Tsubota, and Kazuhiro Kimura. "Brown adipocytes postnatally arise through both differentiation from progenitors and conversion from white adipocytes in Syrian hamster." Journal of Applied Physiology 124, no. 1 (January 1, 2018): 99–108. http://dx.doi.org/10.1152/japplphysiol.00622.2017.
Full textAbstract:
To investigate the postnatal development of brown adipose tissue (BAT) in Syrian hamsters, we histologically examined interscapular fat tissue from 5–16-day-old pups, focusing on how brown adipocytes arise. Interscapular fat of 5-day-old hamsters mainly consisted of white adipocytes containing large unilocular lipid droplets, as observed in typical white adipose tissue (WAT). On day 7, clusters of small, proliferative nonadipocytes with a strong immunoreactivity for Ki67 appeared near the edge of the interscapular fat tissue. The area of the Ki67-positive regions expanded to ~50% of the total tissue area by day 10. The interscapular fat showed the typical BAT feature by day 16. A brown adipocyte-specific marker, uncoupling protein-1, was clearly detected on day 10 and thereafter, while not detected on day 7. During conversion of interscapular fat from WAT to BAT, unilocular adipocytes completely and rapidly disappeared without obvious apoptosis. Dual immunofluorescence staining for Ki67 and monocarboxylate transporter 1 (MCT1), another selective marker for brown adipocytes, revealed that most of the proliferating cells were of the brown adipocyte lineage. Electron microscopic examination showed that some of the white adipocytes contained small lipid droplets in addition to the large droplet and expressed MCT1 as do progenitor and mature brown adipocytes, implying a direct conversion from white to brown adipocytes. These results suggest that BAT of Syrian hamsters develops postnatally through two different pathways: the proliferation and differentiation of brown adipocyte progenitors and the conversion of unilocular adipocytes to multilocular brown adipocytes. NEW & NOTEWORTHY Brown and white adipose tissues (BAT and WAT, respectively) are quite different in morphological features and function; however, the boundary between these tissues is obscure. In this study, we histologically evaluated the process of BAT development in Syrian hamsters, which shows postnatal conversion of WAT to BAT. Our results suggest that brown adipocytes arise through two different pathways: the proliferation and differentiation of brown adipocyte progenitors and the conversion from white adipocytes.
2
Rakhshandehroo, Maryam, Arjen Koppen, and Eric Kalkhoven. "Pref-1 preferentially inhibits heat production in brown adipose tissue." Biochemical Journal 443, no. 3 (April 16, 2012): e3-e5. http://dx.doi.org/10.1042/bj20120382.
Full textAbstract:
In mammals there are two types of adipocytes with opposing functions. Brown adipocytes are characterized by a high number of mitochondria and are specialized for heat production (thermogenesis), expressing thermogenic genes such as UCP1 (uncoupling protein 1). White adipocytes, on the other hand, store energy. Although many key regulators in the differentiation of white adipocytes have been established, our current knowledge on the same proteins in brown adipogenesis is lagging behind. One example is Pref-1 (pre-adipocyte factor-1), which maintains white pre-adipocytes in an undifferentiated state, but is only poorly characterized in the brown pre-adipocyte lineage. In this issue of the Biochemical Journal, Armengol et al. now shed new light on the role and regulation of Pref-1 in brown pre-adipocytes. First, Pref-1 specifically inhibits the thermogenic gene programme in brown pre-adipocytes. Secondly, they identified the transcription factor C/EBPδ (CCAAT/enhancer-binding protein δ) as a direct positive regulator of Pref-1 expression, whereas this protein does not fulfil this role in white adipogenesis. Taken together, these findings indicate that specific manipulation of brown adipocyte differentiation and/or function without interfering with their white adipocyte counterparts may be possible, which may open up new therapeutic ways to combat obesity-associated health problems.
3
Gburcik, Valentina, William P. Cawthorn, Jan Nedergaard, James A. Timmons, and Barbara Cannon. "An essential role for Tbx15 in the differentiation of brown and “brite” but not white adipocytes." American Journal of Physiology-Endocrinology and Metabolism 303, no. 8 (October 15, 2012): E1053—E1060. http://dx.doi.org/10.1152/ajpendo.00104.2012.
Full textAbstract:
The transcription factor Tbx15 is expressed predominantly in brown adipose tissue and in those white adipose depots that are capable of giving rise to brown-in-white (“brite”/“beige”) adipocytes. Therefore, we have investigated a possible role here of Tbx15 in brown and brite adipocyte differentiation in vitro. Adipocyte precursors were isolated from interscapular and axilliary brown adipose tissues, inguinal white (“brite”) adipose tissue, and epididymal white adipose tissue in 129/Sv mouse pups and differentiated in culture. Differentiation was enhanced by chronic treatment with the PPARγ agonist rosiglitazone plus the sympathetic neurotransmitter norepinephrine. Using short interfering RNAs (siRNA) directed toward Tbx15 in these primary adipocyte cultures, we decreased Tbx15 expression >90%. This resulted in reduced expression levels of adipogenesis markers (PPARγ, aP2). Importantly, Tbx15 knockdown reduced the expression of brown phenotypic marker genes (PRDM16, PGC-1α, Cox8b/Cox4, UCP1) in brown adipocytes and even more markedly in inguinal white adipocytes. In contrast, Tbx15 knockdown had no effect on white adipocytes originating from a depot that is not brite competent in vivo (epididymal). Therefore, Tbx15 may be essential for the development of the adipogenic and thermogenic programs in adipocytes/adipomyocytes capable of developing brown adipocyte features.
4
Saggerson, E. D., and Z. Jamal. "Differences in the properties of A1-type adenosine receptors in rat white and brown adipocytes." Biochemical Journal 269, no. 1 (July 1, 1990): 157–61. http://dx.doi.org/10.1042/bj2690157.
Full textAbstract:
1. White adipocytes were found to be more responsive than brown adipocytes to inhibition of lipolysis by the A1 adenosine receptor agonist phenylisopropyladenosine. 2. Radioligand binding studies with plasma membranes isolated from the two adipocyte types indicated differences in the properties of the A1 receptors. Kd values (high and low affinity) for phenylisopropyladenosine were higher in membranes from brown adipocytes. The Kd values for the antagonist dipropylcyclopentylxanthine were also higher in brown adipocyte membranes. 3. The effects of guanine nucleotides in converting adipocyte A1 receptors into a low-affinity state were enhanced by dithiothreitol.
5
Giralt, Marta, and Francesc Villarroya. "White, Brown, Beige/Brite: Different Adipose Cells for Different Functions?" Endocrinology 154, no. 9 (June 19, 2013): 2992–3000. http://dx.doi.org/10.1210/en.2013-1403.
Full textAbstract:
Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis in mammals. Rodent studies indicated that BAT thermogenic activity may protect against obesity. Recent findings using novel radiodiagnosis procedures revealed unanticipated high activity of BAT in adult humans. Moreover, complex processes of cell differentiation leading to the appearance of active brown adipocytes have been recently identified. The brown adipocytes clustered in defined anatomical BAT depots of rodents arise from mesenchymal precursor cells common to the myogenic cell lineage. They are being called “classical” or “developmentally programmed” brown adipocytes. However, brown adipocytes may appear after thermogenic stimuli at anatomical sites corresponding to white adipose tissue (WAT). This process is called the “browning” of WAT. The brown adipocytes appearing in WAT derive from precursor cells different from those in classical BAT and are closer to the white adipocyte cell lineage. The brown adipocytes appearing in WAT are often called “inducible, beige, or brite.” The appearance of these inducible brown adipocytes in WAT may also involve transdifferentiation processes of white-to-brown adipose cells. There is no evidence that the ultimate thermogenic function of the beige/brite adipocytes differs from that of classical brown adipocytes, although some genetic data in rodents suggest a relevant role of the browning process in protection against obesity. Although the activation of classical BAT and the browning process share common mechanisms of induction (eg, noradrenergic-mediated induction by cold), multiple novel adrenergic-independent endocrine factors that activate BAT and the browning of WAT have been identified recently. In adult humans, BAT is mainly composed of beige/brite adipocytes, although recent data indicate the persistence of classical BAT at some anatomical sites. Understanding the biological processes controlling brown adipocyte activity and differentiation could help the design of BAT-focused strategies to increase energy expenditure and fight against obesity.
6
Dowal, Louisa, Pooja Parameswaran, Sarah Phat, Syamala Akella, Ishita Deb Majumdar, Jyoti Ranjan, Chahan Shah, et al. "Intrinsic Properties of Brown and White Adipocytes Have Differential Effects on Macrophage Inflammatory Responses." Mediators of Inflammation 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/9067049.
Full textAbstract:
Obesity is marked by chronic, low-grade inflammation. Here, we examined whether intrinsic differences between white and brown adipocytes influence the inflammatory status of macrophages. White and brown adipocytes were characterized by transcriptional regulation of UCP-1, PGC1α, PGC1β, and CIDEA and their level of IL-6 secretion. The inflammatory profile of PMA-differentiated U937 and THP-1 macrophages, in resting state and after stimulation with LPS/IFN-gamma and IL-4, was assessed by measuring IL-6 secretion and transcriptional regulation of a panel of inflammatory genes after mono- or indirect coculture with white and brown adipocytes. White adipocyte monocultures show increased IL-6 secretion compared to brown adipocytes. White adipocytes cocultured with U937 and THP-1 macrophages induced a greater increase in IL-6 secretion compared to brown adipocytes cocultured with both macrophages. White adipocytes cocultured with macrophages increased inflammatory gene expression in both types. In contrast, macrophages cocultured with brown adipocytes induced downregulation or no alterations in inflammatory gene expression. The effects of adipocytes on macrophages appear to be independent of stimulation state. Brown adipocytes exhibit an intrinsic ability to dampen inflammatory profile of macrophages, while white adipocytes enhance it. These data suggest that brown adipocytes may be less prone to adipose tissue inflammation that is associated with obesity.
7
Giordano, A., M. Morroni, F. Carle, R. Gesuita, G. F. Marchesi, and S. Cinti. "Sensory nerves affect the recruitment and differentiation of rat periovarian brown adipocytes during cold acclimation." Journal of Cell Science 111, no. 17 (September 1, 1998): 2587–94. http://dx.doi.org/10.1242/jcs.111.17.2587.
Full textAbstract:
Rat periovarian adipose tissue contains a low number of uncoupling protein-expressing brown adipocytes scattered into lobules of white fat. Their increase following cold acclimation is matched by a major increase in noradrenergic and neuropeptide Y-, substance P- and calcitonin gene-related peptide-containing nerves. To ascertain whether periovarian fat is provided with sensory nerves, and whether any relationship exists between such nerves (in particular the calcitonin gene-related peptide-containing fibers found in cold-acclimated rats in close association with brown adipocytes) and brown fat recruitment, the effects of capsaicin desensitization on neuropeptide-containing nerves and brown adipocyte density were studied in the periovarian tissue of rats kept at 20 degrees C and on a group acclimated to 4 degrees C for 14 days. In both groups, systemic capsaicin administration considerably reduced the expression of substance P and calcitonin gene-related peptide in vascular-nerve bundles and parenchyma. In cold-acclimated rats, the increase in brown adipocyte density was significantly checked by capsaicin administration (21.11 versus 7.96 brown adipocytes/mm2, P<0.05). Finally, ultrastructural investigation showed the occurrence of brown adipocyte precursors filled with aggregates of glycogen and poorly differentiated multilocular adipocytes in capsaicin-treated cold-acclimated rats. These data suggest that periovarian adipose tissue is indeed provided with sensory neuropeptide-containing nerves and that they play a role in the recruitment and differentiation of brown adipocytes.
8
Lizcano, Fernando, and Diana Vargas. "Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity." International Journal of Endocrinology 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/9542061.
Full textAbstract:
All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.
9
Rajan, Sujith, Kripa Shankar, Muheeb Beg, Salil Varshney, Abhishek Gupta, Ankita Srivastava, Durgesh Kumar, et al. "Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte." Journal of Endocrinology 230, no. 3 (September 2016): 275–90. http://dx.doi.org/10.1530/joe-16-0099.
Full textAbstract:
The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes.
10
Baht, H. S., and E. D. Saggerson. "Comparison of triacylglycerol synthesis in rat brown and white adipocytes. Effects of hypothyroidism and streptozotocin-diabetes on enzyme activities and metabolic fluxes." Biochemical Journal 250, no. 2 (March 1, 1988): 325–33. http://dx.doi.org/10.1042/bj2500325.
Full textAbstract:
1. Adipocytes were isolated from the interscapular brown fat and the epididymal white fat of normal, streptozotocin-diabetic and hypothyroid rats. 2. Measurements were made of the maximum rate of triacylglycerol synthesis by monitoring the incorporation of [U-14C]glucose into acylglycerol glycerol in the presence of palmitate (1 mM) and insulin (4 nM) and of the activities of the following triacylglycerol-synthesizing enzymes: fatty acyl-CoA synthetase (FAS), mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), dihydroxyacetonephosphate acyltransferase (DHAPAT), monoacylglycerol phosphate acyltransferase (MGPAT), Mg2+-dependent phosphatidate phosphohydrolase (PPH) and diacylglycerol acyltransferase (DGAT). 3. FAS activity in brown adipocytes was predominantly localized in the mitochondrial fraction, whereas a microsomal localization of this enzyme predominated in white adipocytes. Subcellular distributions of the other enzyme activities in brown adipocytes were similar to those shown previously with white adipocytes [Saggerson, Carpenter, Cheng & Sooranna (1980) Biochem. J. 190, 183-189]. 4. Relative to cell DNA, brown adipocytes had lower activities of triacylglycerol-synthesizing enzymes and showed lower rates of metabolic flux into acylglycerols than did white adipocytes isolated from the same animals. 5. Diabetes decreased both metabolic flux into acylglycerols and the activities of triacylglycerol-synthesizing enzymes in white adipocytes. By contrast, although diabetes decreased metabolic flux into brown-adipocyte acylglycerols by 80%, there were no decreases in the activities of triacylglycerol-synthesizing enzymes, and the activity of PPH was significantly increased. 6. Hypothyroidism increased metabolic flux into acylglycerols in both cell types, and increased activities of all triacylglycerol-synthesizing enzymes in brown adipocytes. By contrast, in white adipocytes, although hypothyroidism increased the activities of FAS, microsomal GPAT and DGAT, this condition decreased the activities of mitochondrial GPAT and PPH. 7. It was calculated that the maximum capabilities for fatty acid oxidation and esterification are approximately equal in brown adipocytes. In white adipocytes esterification is predominant by approx. 100-fold. 8. Diabetes almost abolished incorporation of [U-14C]glucose into fatty acids in both adipocyte types. Hypothyroidism increased fatty acid synthesis in white and brown adipocytes by 50% and 1000% respectively.
11
Cadrin, M., M. Tolszczuk, J. Guy, G. Pelletier, K. B. Freeman, and L. J. Bukowiecki. "Immunohistochemical identification of the uncoupling protein in rat brown adipose tissue." Journal of Histochemistry & Cytochemistry 33, no. 2 (February 1985): 150–54. http://dx.doi.org/10.1177/33.2.3881519.
Full textAbstract:
Brown adipose tissue mitochondria are characterized by the presence of an uncoupling protein that gives them an exceptional capacity for substrate-controlled respiration and thermogenesis. The specific localization of this protein in rat brown adipocytes was demonstrated using an immunohistochemical technique, the peroxidase-antiperoxidase (PAP) method. Light microscopy observations showed that serum antibodies raised against the uncoupling protein selectively reacted with multilocular brown adipocytes. No labeling could be detected in either unilocular adipocytes, capillaries, or muscle fibers (striated and vascular smooth muscle). Staining was more intensive in certain adipocytes than in others, suggesting the presence of cellular heterogeneity. The specificity of the staining technique was demonstrated by showing that treatment of the preparations with antiserum saturated with an excess of uncoupling protein almost entirely inhibited brown adipocyte labeling. The specificity and selectivity of the PAP method allow the clear differentiation of uncoupling protein-containing adipocytes from other cellular types, suggesting that this immunohistochemical technique will represent an extremely useful tool for studying adipocyte function and differentiation.
12
Ussar, Siegfried, Kevin Y. Lee, Simon N. Dankel, Jeremie Boucher, Max-Felix Haering, Andre Kleinridders, Thomas Thomou, et al. "ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes." Science Translational Medicine 6, no. 247 (July 30, 2014): 247ra103. http://dx.doi.org/10.1126/scitranslmed.3008490.
Full textAbstract:
White, beige, and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige, and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vitro, and in vivo methods, we have identified three new cell surface markers of adipose cell types. The amino acid transporter ASC-1 is a white adipocyte–specific cell surface protein, with little or no expression in brown adipocytes, whereas the amino acid transporter PAT2 and the purinergic receptor P2RX5 are cell surface markers expressed in classical brown and beige adipocytes in mice. These markers also selectively mark brown/beige and white adipocytes in human tissue. Thus, ASC-1, PAT2, and P2RX5 are membrane surface proteins that may serve as tools to identify and target white and brown/beige adipocytes for therapeutic purposes.
13
Münzberg, Heike, Elizabeth Floyd, and Ji Suk Chang. "Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?" Physiology 36, no. 4 (July 1, 2021): 246–55. http://dx.doi.org/10.1152/physiol.00038.2020.
Full textAbstract:
Obesity research progresses in understanding neuronal circuits and adipocyte biology to regulate metabolism. However, the interface of neuro-adipocyte interaction is less studied. We summarize the current knowledge of adipose tissue innervation and interaction with adipocytes and emphasize adipocyte transitions from white to brown adipocytes and vice versa. We further highlight emerging concepts for the differential neuronal regulation of brown/beige versus white adipocyte and the interdependence of both for metabolic regulation.
14
Lizcano, Fernando. "The Beige Adipocyte as a Therapy for Metabolic Diseases." International Journal of Molecular Sciences 20, no. 20 (October 12, 2019): 5058. http://dx.doi.org/10.3390/ijms20205058.
Full textAbstract:
Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.
15
Nanduri, Ravikanth. "Epigenetic Regulators of White Adipocyte Browning." Epigenomes 5, no. 1 (January 12, 2021): 3. http://dx.doi.org/10.3390/epigenomes5010003.
Full textAbstract:
Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes.
16
Xue, Ruidan, Yun Wan, Shuo Zhang, Qiongyue Zhang, Hongying Ye, and Yiming Li. "Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes." American Journal of Physiology-Endocrinology and Metabolism 306, no. 4 (February 15, 2014): E363—E372. http://dx.doi.org/10.1152/ajpendo.00119.2013.
Full textAbstract:
There are two different types of fat present in mammals: white adipose tissue, the primary site of energy storage, and brown adipose tissue, which is specializes in energy expenditure. Factors that specify the developmental fate and function of brown fat are poorly understood. Bone morphogenic proteins (BMPs) play an important role in adipogenesis. While BMP4 is capable of triggering commitment of stem cells to the white adipocyte lineage, BMP7 triggers commitment of progenitor cells to a brown adipocyte lineage and activates brown adipogenesis. To investigate the differential effects of BMPs on the development of adipocytes, C3H10T1/2 pluripotent cells were pretreated with BMP4 and BMP7, followed by different adipogenic induction cocktails. Both BMP4 and BMP7 unexpectedly activated a full program of brown adipogenesis, including induction of the brown fat-defining marker uncoupling protein-1 (UCP1), increasing the expression of early regulators of brown fat fate PRDM16 (PR domain-containing 16) and induction of mitochondrial biogenesis and function. Implantation of BMP4-pretreated C3H10T1/2 cells into nude mice resulted in the development of adipose tissue depots containing UCP1-positive brown adipocytes. Interestingly, BMP4 could also induce brown fat-like adipocytes in both white and brown preadipocytes, thereby decreasing the classical brown adipocyte marker Zic1 and increasing the recently identified beige adipocyte marker TMEM26. The data indicate an important role for BMP4 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro and offers a potentially new therapeutic approach for the treatment of obesity.
17
Roncero, C., M. Lorenzo, and M. Benito. "Regulation of rat foetal lipogenesis in brown adipose tissue in vivo and in isolated brown adipocytes during the last day of, and after prolonged, gestation." Biochemical Journal 243, no. 2 (April 15, 1987): 617–20. http://dx.doi.org/10.1042/bj2430617.
Full textAbstract:
Rates of lipogenesis in foetal isolated brown adipocytes from 22-day-pregnant rats were significantly increased by lactate plus pyruvate as major substrates in the incubation medium, in comparison with the endogenous rates. Insulin stimulated foetal brown-adipocyte lipogenesis, and adrenaline or noradrenaline and isoprenaline decreased lipogenesis. Glucagon had no effect on the lipogenic rate in brown adipocytes. Progesterone administration to the mother significantly increased the rates of lipogenesis in brown adipose tissue and in isolated brown adipocytes from 22-day foetuses. Prolongation of gestation by progesterone to day 23 decreased the rates of brown-adipose-tissue lipogenesis in vivo and in isolated cells in the post-mature foetuses.
18
Kutyavin, Vassily I., and Ajay Chawla. "BCL6 regulates brown adipocyte dormancy to maintain thermogenic reserve and fitness." Proceedings of the National Academy of Sciences 116, no. 34 (August 2, 2019): 17071–80. http://dx.doi.org/10.1073/pnas.1907308116.
Full textAbstract:
Brown adipocytes provide a metabolic defense against environmental cold but become dormant as mammals habituate to warm environments. Although dormancy is a regulated response in brown adipocytes to environmental warmth, its transcriptional mechanisms and functional importance are unknown. Here, we identify B cell leukemia/lymphoma 6 (BCL6) as a critical regulator of dormancy in brown adipocytes but not for their commitment, differentiation, or cold-induced activation. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic fitness during dormancy. Mechanistically, BCL6 remodels the epigenome of brown adipocytes to enforce brown and oppose white adipocyte cellular identity. Thus, unlike other thermogenic regulators, BCL6 is specifically required for maintaining thermogenic fitness when mammals acclimate to environmental warmth.
19
Winther, Sally, Marie S. Isidor, Astrid L. Basse, Nina Skjoldborg, Amanda Cheung, Bjørn Quistorff, and Jacob B. Hansen. "Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption." American Journal of Physiology-Endocrinology and Metabolism 314, no. 3 (March 1, 2018): E214—E223. http://dx.doi.org/10.1152/ajpendo.00218.2017.
Full textAbstract:
During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation. Knockdown of glucose transporters in brown adipocytes not only impaired ISO-stimulated glycolytic flux but also oxygen consumption. Diminishing glycolytic flux by knockdown of the first and final enzyme of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways.
20
Saggerson, E. D., T. W. J. McAllister, and H. S. Baht. "Lipogenesis in rat brown adipocytes. Effects of insulin and noradrenaline, contributions from glucose and lactate as precursors and comparisons with white adipocytes." Biochemical Journal 251, no. 3 (May 1, 1988): 701–9. http://dx.doi.org/10.1042/bj2510701.
Full textAbstract:
1. Brown adipocytes were isolated from the interscapular depot of male rats maintained at approx. 21 degrees C. In some experiments parallel studies were made with white adipocytes from the epididymal depot. 2. Insulin increased and noradrenaline decreased [U-14C]glucose incorporation into fatty acids by brown adipocytes. Brown adipocytes differed from white adipocytes in that exogenous fatty acid (palmitate) substantially decreased fatty acid synthesis from glucose. Both noradrenaline and insulin increased lactate + pyruvate formation by brown adipocytes. Brown adipocytes converted a greater proportion of metabolized glucose into lactate + pyruvate and a smaller proportion into fatty acids than did white adipocytes. 3. In brown adipocytes, when fatty acid synthesis from [U-14C]glucose was decreased by noradrenaline or palmitate, incorporation of 3H2O into fatty acids was also decreased to an extent which would not support proposals for extensive recycling into fatty acid synthesis of acetyl-CoA derived from fatty acid oxidation. 4. In the absence of glucose, [U-14C]lactate was a poor substrate for lipogenesis in brown adipocytes, but its use was facilitated by glucose. When brown adipocytes were incubated with 1 mM-lactate + 5 mM-glucose, lactate-derived carbon generally provided at least 50% of the precursor for fatty acid synthesis. 5. Both insulin and noradrenaline increased [U-14C]glucose conversion into CO2 by brown adipocytes (incubated in the presence of lactate) and, in combination, stimulation of glucose oxidation by these two agents showed synergism. Rates of 14CO2 formation from glucose by brown adipocytes were relatively small compared with maximum rates of oxygen consumption by these cells, suggesting that glucose is unlikely to be a major substrate for thermogenesis. 6. Brown adipocytes from 6-week-old rats had considerably lower maximum rates of fatty acid synthesis, relative to cell DNA content, than white adipocytes. By contrast, rates of fatty acid synthesis from 3H2O in vivo were similar in the interscapular and epididymal fat depots. Expressed relative to activities of fatty acid synthase or ATP citrate lyase, however, brown adipocytes synthesized fatty acids as effectively as did white adipocytes. It is suggested that the cells most active in fatty acid synthesis in the brown adipose tissue are not recovered fully in the adipocyte fraction during cell isolation. Differences in rates of fatty acid synthesis between brown and white adipocytes were less apparent at 10 weeks of age.
21
Cedikova, Miroslava, Michaela Kripnerová, Jana Dvorakova, Pavel Pitule, Martina Grundmanova, Vaclav Babuska, Dana Mullerova, and Jitka Kuncova. "Mitochondria in White, Brown, and Beige Adipocytes." Stem Cells International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/6067349.
Full textAbstract:
Mitochondria play a key role in energy metabolism in many tissues, including cardiac and skeletal muscle, brain, liver, and adipose tissue. Three types of adipose depots can be identified in mammals, commonly classified according to their colour appearance: the white (WAT), the brown (BAT), and the beige/brite/brown-like (bAT) adipose tissues. WAT is mainly involved in the storage and mobilization of energy and BAT is predominantly responsible for nonshivering thermogenesis. Recent data suggest that adipocyte mitochondria might play an important role in the development of obesity through defects in mitochondrial lipogenesis and lipolysis, regulation of adipocyte differentiation, apoptosis, production of oxygen radicals, efficiency of oxidative phosphorylation, and regulation of conversion of white adipocytes into brown-like adipocytes. This review summarizes the main characteristics of each adipose tissue subtype and describes morphological and functional modifications focusing on mitochondria and their activity in healthy and unhealthy adipocytes.
22
Hu, Jiamiao, Arong Zhou, Peter C. K. Cheung, Baodong Zheng, Shaoxiao Zeng, and Shaoling Lin. "Expression of GPR43 in Brown Adipogenesis Is Enhanced by Rosiglitazone and Controlled by PPARγ/RXR Heterodimerization." PPAR Research 2018 (2018): 1–8. http://dx.doi.org/10.1155/2018/1051074.
Full textAbstract:
GPR43, a G-protein coupled receptor recognizing short-chain fatty acids, has been reported to participate in many biological functions of white adipocytes, such as adipogenesis and lipolysis. However, the functional role of GPR43 in brown adipocytes is still not clear. In this study, we investigated the effects of the PPARγ agonist rosiglitazone on GPR43 expression in brown adipogenesis. The results demonstrated that GPR43 was expressed during the late phase of brown adipocyte differentiation, which could be further augmented by adipogenic agent rosiglitazone treatment. The PPARγ/RXR heterodimerization was found to be the key transcription factor for this enhancing effect of rosiglitazone on GPR43 expression. Taken together, these results suggested GPR43 levels might be regulated by PPARγ-activated events during brown adipocytes differentiation and reflect the adipogenesis status of brown adipocytes.
23
Karlina, Ruth, Dominik Lutter, Viktorian Miok, David Fischer, Irem Altun, Theresa Schöttl, Kenji Schorpp, et al. "Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice." Life Science Alliance 4, no. 1 (November 30, 2020): e202000924. http://dx.doi.org/10.26508/lsa.202000924.
Full textAbstract:
Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.
24
Li, Yongguo, David Lasar, Tobias Fromme, and Martin Klingenspor. "White, brite, and brown adipocytes: the evolution and function of a heater organ in mammals." Canadian Journal of Zoology 92, no. 7 (July 2014): 615–26. http://dx.doi.org/10.1139/cjz-2013-0165.
Full textAbstract:
Brown fat is a specialized heater organ in eutherian mammals. In contrast to the energy storage function of white adipocytes, brown adipocytes dissipate nutrient energy by uncoupling of mitochondrial oxidative phosphorylation, which depends on uncoupling protein 1 (UCP1). UCP1, as well as UCP2 and UCP3, belong to the family of mitochondrial carriers inserted into the inner mitochondrial membrane for metabolite trafficking between the matrix and the intermembrane space. UCP1 transports protons into the mitochondrial matrix when activated by a rise in free fatty acid levels in the cell. This UCP1-dependant proton leak drives high oxygen consumption rates in the absence of ATP synthesis and dissipates proton motive force as heat. The enormous heating capacity of brown fat is supported by dense vascularization, high rates of tissue perfusion, and high mitochondrial density in brown adipocytes. It has been known for more than 50 years that nonshivering thermogenesis in brown fat serves to maintain body temperature of neonates and small mammals in cold environments, and is used by hibernators for arousal from torpor. It has been speculated that the development of brown fat as a new source for nonshivering thermogenesis provided mammals with a unique advantage for survival in the cold. Indeed brown fat and UCP1 is found in ancient groups of mammals, like the afrotherians and marsupials. In the latter, however, the thermogenic function of UCP1 and brown fat has not been demonstrated as of yet. Notably, orthologs of all three mammalian UCP genes are also present in the genomes of bony fishes and in amphibians. Molecular phylogeny reveals a striking increase in the substitution rate of UCP1 between marsupial and eutherian lineages. At present, it seems that UCP1 only gained thermogenic function in brown adipocytes of eutherian mammals, whereas the function of UCP1 and that of the other UCPs in ectotherms remains to be identified. Evolution of thermogenic function required expression of UCP1 in a brown-adipocyte-like cell equipped with high mitochondrial density embedded in a well-vascularized tissue. Brown-adipocyte-like cells in white adipose tissue, called “brite” (brown-in-white) or “beige” adipocytes, emerge during adipogenesis and in response to cold exposure in anatomically distinct adipose tissue depots of juvenile and adult rodents. These brite adipocytes may resemble the archetypical brown adipocyte in vertebrate evolution. It is therefore of interest to elucidate the molecular mechanisms of brite adipocyte differentiation, study the bioenergetic properties of these cells, and search for the presence of related brown-adipocyte-like cells in nonmammalian vertebrates.
25
Baht, H. S., and E. D. Saggerson. "A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism." Biochemical Journal 251, no. 2 (April 15, 1988): 553–57. http://dx.doi.org/10.1042/bj2510553.
Full textAbstract:
1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.
26
Armengol, Jordi, Josep A. Villena, Elayne Hondares, María C. Carmona, Hei Sook Sul, Roser Iglesias, Marta Giralt, and Francesc Villarroya. "Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ." Biochemical Journal 443, no. 3 (April 16, 2012): 799–810. http://dx.doi.org/10.1042/bj20111714.
Full textAbstract:
Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) α-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPδ activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPδ knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPδ in C/EBPα-null BAT and high expression of C/EBPδ in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPδ and strongly impaired expression of the thermogenic markers UCP1 and PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-α]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPδ as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation.
27
Bukowiecki, L. J., A. Geloen, and A. J. Collet. "Proliferation and differentiation of brown adipocytes from interstitial cells during cold acclimation." American Journal of Physiology-Cell Physiology 250, no. 6 (June 1, 1986): C880—C887. http://dx.doi.org/10.1152/ajpcell.1986.250.6.c880.
Full textAbstract:
The mechanisms of brown adipocyte proliferation and differentiation during cold acclimation (and/or adaptation to hyperphagia) have been studied by quantitative photonic radioautography. [3H]thymidine was injected to warm-acclimated (25 degrees C) rats and to animals exposed to 5 degrees C for 2 days. Samples of interscapular brown adipose tissue were collected for quantitative analysis of mitotic frequencies at various periods of time (4 h-15 days) after the injection of [3H]thymidine, the rats being maintained at the temperatures to which they were initially exposed. Confirming our previous results [Bukowiecki et al., Am. J. Physiol. 242 (Endocrinol. Metab. 5): E353-E359, 1982], it was found that cold exposure for 2 days markedly enhanced mitotic activity in endothelial cells, interstitial cells, and brown preadipocytes rather than in fully differentiated brown adipocytes. The total tissue labeling index (percent of labeled nuclei) increased approximately 70 times over control values. We now report that cellular labeling progressively increased in mature brown adipocytes during cold acclimation, whereas it correspondingly decreased in interstitial cells and brown preadipocytes. This indicates that the sequence of events for cellular differentiation is interstitial cells----brown preadipocytes----mature brown adipocytes. Remarkable, labeling frequency did not change in endothelial cells during cold acclimation demonstrating that these cells cannot be considered as progenitors of brown adipocytes. It is suggested that brown adipocyte proliferation and differentiation from interstitial cells represent the fundamental phenomena explaining the enhanced capacity of cold-acclimated and/or hyperphagic rats to respond calorigenically to catecholamines.
28
Moon, Hanbyeol, Jung-Won Choi, Byeong-Wook Song, Il-Kwon Kim, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang, and Sang Woo Kim. "Isoliquiritigenin Enhances the Beige Adipocyte Potential of Adipose-Derived Stem Cells by JNK Inhibition." Molecules 25, no. 23 (December 1, 2020): 5660. http://dx.doi.org/10.3390/molecules25235660.
Full textAbstract:
Human adipose-derived stem cells (hASCs) can be isolated from fat tissue and have attracted interest for their potential therapeutic applications in metabolic disease. hASCs can be induced to undergo adipogenic differentiation in vitro by exposure to chemical agents or inductive growth factors. We investigated the effects and mechanism of differentiating hASC-derived white adipocytes into functional beige and brown adipocytes with isoliquiritigenin (ILG) treatment. Here, we showed that hASC-derived white adipocytes could promote brown adipogenesis by expressing both uncoupling protein 1 (UCP1) and PR/SET Domain 16 (PRDM16) following low-dose ILG treatments. ILG treatment of white adipocytes enhanced the expression of brown fat-specific markers, while the expression levels of c-Jun N-terminal kinase (JNK) signaling pathway proteins were downregulated. Furthermore, we showed that the inhibition of JNK phosphorylation contributed to white adipocyte differentiation into beige adipocytes, which was validated by the use of SP600125. We identified distinct regulatory effects of ILG dose responses and suggested that low-dose ILG induced the beige adipocyte potential of hASCs via JNK inhibition.
29
Corrêa, Heyn, and Magalhaes. "The Impact of the Adipose Organ Plasticity on Inflammation and Cancer Progression." Cells 8, no. 7 (June 30, 2019): 662. http://dx.doi.org/10.3390/cells8070662.
Full textAbstract:
Obesity is characterized by chronic and low-grade systemic inflammation, an increase of adipose tissue, hypertrophy, and hyperplasia of adipocytes. Adipose tissues can be classified into white, brown, beige and pink adipose tissues, which display different regulatory, morphological and functional characteristics of their adipocyte and immune cells. Brown and white adipocytes can play a key role not only in the control of energy homeostasis, or through the balance between energy storage and expenditure, but also by the modulation of immune and inflammatory responses. Therefore, brown and white adipocytes can orchestrate important immunological crosstalk that may deeply impact the tumor microenvironment and be crucial for cancer establishment and progression. Recent works have indicated that white adipose tissues can undergo a process called browning, in which an inducible brown adipocyte develops. In this review, we depict the mechanisms involved in the differential role of brown, white and pink adipocytes, highlighting their structural, morphological, regulatory and functional characteristics and correlation with cancer predisposition, establishment, and progression. We also discuss the impact of the increased adiposity in the inflammatory and immunological modulation. Moreover, we focused on the plasticity of adipocytes, describing the molecules produced and secreted by those cells, the modulation of the signaling pathways involved in the browning phenomena of white adipose tissue and its impact on inflammation and cancer.
30
Zilberfarb, V., F. Pietri-Rouxel, R. Jockers, S. Krief, C. Delouis, T. Issad, and A. D. Strosberg. "Human immortalized brown adipocytes express functional beta3-adrenoceptor coupled to lipolysis." Journal of Cell Science 110, no. 7 (April 1, 1997): 801–7. http://dx.doi.org/10.1242/jcs.110.7.801.
Full textAbstract:
Human brown pre-adipocytes were immortalized by microinjection of the genes encoding simian virus 40 T and t antigens under the control of the human vimentin promotor. The transfected pre-adipocytes were cultured for several months with no loss of their morphological characteristics. These cells accumulate lipids and differentiate into adipocytes when treated with insulin, triiodothyronine and dexamethazone. The mRNA of various adipocyte markers was detected by reverse transcriptase-polymerase chain reaction analysis, including hormone-sensitive lipase, lipoprotein lipase, adipsin, glucose transporters 1 and 4, the uncoupling protein (specific of brown adipocytes), and leptin, the product of the ob gene. Pharmacological analyses indicated that the beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in PAZ6 cells and that this receptor subtype is functionally coupled to adenylate cyclase and lipolysis. The immortalization of human adipocytes will permit pharmacological analysis of the human beta3-adrenoceptor function in adipose cells and will allow detailed studies of human adipocyte differentiation.
31
Hartig, Sean M., David A. Bader, Kathleen V. Abadie, Massoud Motamed, Mark P. Hamilton, Weiwen Long, Brian York, et al. "Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes." Molecular Endocrinology 29, no. 9 (September 1, 2015): 1320–33. http://dx.doi.org/10.1210/me.2015-1084.
Full textAbstract:
Abstract Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis.
32
Zhang, Wen-Chao, Feng Qin, Xiao-Jun Wang, Zhi-Fei Liu, Lin Zhu, Ang Zeng, Ming-Zi Zhang, Nan-Ze Yu, and Xiao Long. "Adipose-Derived Stromal Cells Attenuate Adipose Inflammation in Obesity through Adipocyte Browning and Polarization of M2 Macrophages." Mediators of Inflammation 2019 (December 4, 2019): 1–10. http://dx.doi.org/10.1155/2019/1731540.
Full textAbstract:
Obesity is a metabolic condition associated with multiple health problems such as endocrine and metabolic dysfunction and chronic inflammation in adipose tissues. In this study, the ADSCs could be stimulated to differentiate into brown adipocyte with rosiglitazone treatment based on the Oil-Red-O staining trial. Furthermore, the multilocular lipid droplets located in the center was increased in differentiated brown adipocytes, and brown fat-associated proteins, UCP1, PPAR-γ, and LPL were highly expressed in brown adipocytes differentiated from ADSCs. Additionally, the results of animal experiments showed that both weight and amount of VLDL and LDL were decreased in the serum of obese mice after transplantation of rosiglitazone-induced brown adipocytes, while the level of HDL increased. Moreover, the proteins associated with lipid metabolism, LPA and UCP1, were downregulated, and the inflammatory response was suppressed through inhibition of the ITGAM/NF-κB-mediated proinflammatory responses and polarization of M2 macrophages. Similarly, the amounts of proinflammatory cytokines, TNF-α, IL-6, and IL-1β were decreased after rosiglitazone-induced brown adipocyte transplantation. On the contrary, anti-inflammatory cytokine IL-10 was significantly increased in both groups of obese mice, with or without brown adipocyte transplantation. Therefore, the adipose-derived stromal cells with induced browning could promote lipid consumption and alternative polarization of M2 macrophages to attenuate adipose inflammation in obesity mouse models, which thus provides a potential therapy for obesity.
33
Barbatelli, G., I. Murano, L. Madsen, Q. Hao, M. Jimenez, K. Kristiansen, J. P. Giacobino, R. De Matteis, and S. Cinti. "The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation." American Journal of Physiology-Endocrinology and Metabolism 298, no. 6 (June 2010): E1244—E1253. http://dx.doi.org/10.1152/ajpendo.00600.2009.
Full textAbstract:
The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had a mixed mitochondrioma with classic “brown” and “white” mitochondria, suggesting intermediate steps in the process of direct transformation of white into brown adipocytes (transdifferentiation). Quantitative electron microscopy disclosed that cold exposure (6°C for 10 days) did not induce an increase in WAT preadipocytes. β3-adrenoceptor-knockout mice had a blunted brown adipocyte occurrence upon cold acclimatization. Administration of the β3-adrenoceptor agonist CL316,243 induced the occurrence of brown adipocytes, with the typical morphological features found after cold acclimatization. In contrast, administration of the β1-adrenoceptor agonist xamoterol increased only the number of preadipocytes. These findings indicate that transdifferentiation depends on β3-adrenoceptor activation, whereas preadipocyte recruitment is mediated by β1-adrenoceptor. RT-qPCR experiments disclosed that cold exposure induced enhanced expression of the thermogenic genes and of genes expressed selectively in brown adipose tissue (iBAT) and in both interscapular BAT and WAT. β3-adrenoceptor suppression blunted their expression only in WAT. Furthermore, cold acclimatization induced an increased WAT expression of the gene coding for C/EBPα (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects β3-adrenoceptor-mediated transdifferentiation.
34
Kang, Sona, Laszlo Bajnok, Kenneth A. Longo, Rasmus K. Petersen, Jacob B. Hansen, Karsten Kristiansen, and Ormond A. MacDougald. "Effects of Wnt Signaling on Brown Adipocyte Differentiation and Metabolism Mediated by PGC-1α." Molecular and Cellular Biology 25, no. 4 (February 15, 2005): 1272–82. http://dx.doi.org/10.1128/mcb.25.4.1272-1282.2005.
Full textAbstract:
ABSTRACT Activation of canonical Wnt signaling inhibits brown adipogenesis of cultured cells by impeding induction of PPARγ and C/EBPα. Although enforced expression of these adipogenic transcription factors restores lipid accumulation and expression of FABP4 in Wnt-expressing cells, additional expression of PGC-1α is required for activation of uncoupling protein 1 (UCP1). Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a β3-agonist. In differentiated brown adipocytes, activation of Wnt signaling suppresses expression of UCP1 through repression of PGC-1α. Consistent with these in vitro observations, UCP1-Wnt10b transgenic mice, which express Wnt10b in interscapular tissue, lack functional brown adipose tissue. While interscapular tissue of UCP1-Wnt10b mice lacks expression of PGC-1α and UCP1, the presence of unilocular lipid droplets and expression of white adipocyte genes suggest conversion of brown adipose tissue to white. Reciprocal expression of Wnt10b with UCP1 and PGC-1α in interscapular tissue from cold-challenged or genetically obese mice provides further evidence for regulation of brown adipocyte metabolism by Wnt signaling. Taken together, these data suggest that activation of canonical Wnt signaling early in differentiation blocks brown adipogenesis, whereas activating Wnt signaling in mature brown adipocytes stimulates their conversion to white adipocytes.
35
Shelby, Sarah, Saeed Ghnaimawi, Jinglong Chen, and Yan Huang. "PSVIII-2 Effects of metformin on white adipose tissue transdifferentiation." Journal of Animal Science 97, Supplement_3 (December 2019): 304. http://dx.doi.org/10.1093/jas/skz258.613.
Full textAbstract:
Abstract Early piglet mortality due to chilling is a leading cause of economic loss in swine production. Non-shivering thermogenesis can be used by piglets to increase survivability through the utilization of brown adipose tissue (BAT). Recent studies suggest metformin hydrochloride induces “browning,” or transdifferentiation, of white adipocytes into brown adipocytes and increases BAT formation. Uncoupling proteins (UPC) are the principal markers of BAT. Sow treatment with metformin may increase BAT deposition in neonatal piglets. The objective of this study was to determine if metformin contributed to the expression of brown adipocyte markers UCP1, PRDM16, and PGC1α. To further investigate this, mouse 3T3 adipocyte cells were cultured, subdivided into two 6-well plates, and differentiated into mature white adipocytes. Oil Red O staining confirmed mature adipocytes with the presence of large lipid droplets. The experimental group was treated with 1.25 mM metformin hydrochloride (MET). The control group received only the growth medium (CON). The OD260nm/OD280nm was used to assess the quality of the extracted RNA. PCR analysis showed a significant difference in the expression of UCP1 of the MET cells (P < 0.05). PRDM16 and PGC1α expression showed no significant difference in the two groups (P > 0.10). These results indicate that metformin treatment at 1.25 mM contributed to the upregulation of UCP1 and the transdifferentiation of white adipocytes into brown adipocytes. This suggests the potential use of metformin in the upregulation of UCP to induce BAT formation.
36
Valverde, Angela M., Cecilia Mur, Michael Brownlee, and Manuel Benito. "Susceptibility to Apoptosis in Insulin-like Growth Factor-I Receptor-deficient Brown Adipocytes." Molecular Biology of the Cell 15, no. 11 (November 2004): 5101–17. http://dx.doi.org/10.1091/mbc.e03-11-0853.
Full textAbstract:
Fetal brown adipocytes are insulin-like growth factor-I (IGF-I) target cells. To assess the importance of the IGF-I receptor (IGF-IR) in brown adipocytes during fetal life, we have generated immortalized brown adipocyte cell lines from the IGF-IR-/- mice. Using this experimental model, we demonstrate that the lack of IGF-IR in fetal brown adipocytes increased the susceptibility to apoptosis induced by serum withdrawal. Culture of cells in the absence of serum and growth factors produced rapid DNA fragmentation (4 h) in IGF-IR-/- brown adipocytes, compared with the wild type (16 h). Consequently, cell viability was decreased more rapidly in fetal brown adipocytes in the absence of IGF-IR. Furthermore, caspase-3 activity was induced much earlier in cells lacking IGF-IR. At the molecular level, IGF-IR deficiency in fetal brown adipocytes altered the balance of the expression of several proapoptotic (Bcl-xS and Bim) and antiapoptotic (Bcl-2 and Bcl-xL) members of the Bcl-2 family. This imbalance was irreversible even though in IGF-IR-reconstituted cells. Likewise, cytosolic cytochrome c levels increased rapidly in IGF-IR-deficient cells compared with the wild type. A rapid entry of Foxo1 into the nucleus accompanied by a rapid exit from the cytosol and an earlier activation of caspase-8 were observed in brown adipocytes lacking IGF-IR upon serum deprivation. Activation of caspase-8 was inhibited by 50% in both cell types by neutralizing anti-Fas-ligand antibody. Adenoviral infection of wild-type brown adipocytes with constitutively active Foxol (ADA) increased the expression of antiapoptotic genes, decreased Bcl-xL and induced caspase-8 and -3 activities, with the final outcome of DNA fragmentation. Up-regulation of uncoupling protein-1 (UCP-1) expression in IGF-IR-deficient cells by transduction with PGC-1α or UCP-1 ameliorated caspase-3 activation, thereby retarding apoptosis. Finally, insulin treatment prevented apoptosis in both cell types. However, the survival effect of insulin on IGF-IR-/- brown adipocytes was elicited even in the absence of phosphatidylinositol 3-kinase/Akt signaling. Thus, our results demonstrate for the first time the unique role of IGF-IR in maintaining the balance of death and survival in fetal brown adipocytes.
37
Meiliana, Anna, and Andi Wijaya. "Brown and Beige Fat: Therapeutic Potential in Obesity." Indonesian Biomedical Journal 6, no. 2 (August 1, 2014): 65. http://dx.doi.org/10.18585/inabj.v6i2.32.
Full textAbstract:
BACKGROUND: The epidemic of obesity and type 2 diabetes presents a serious challenge to scientific and biomedical communities worldwide. There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function.CONTENT: Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible ‘brown-like’ adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.SUMMARY: The complexity of adipose tissue presents numerous challenges but also several opportunities for therapeutic intervention. There is persuasive evidence from animal models that enhancement of the function of brown adipocytes, beige adipocytes or both in humans could be very effective for treating type 2 diabetes and obesity. Moreover, there are now an extensive variety of factors and pathways that could potentially be targeted for therapeutic effects. In particular, the discoveries of circulating factors, such as irisin, fibroblast growth factor (FGF)21 and natriuretic peptides, that enhance brown and beige fat function in mice have garnered tremendous interest. Certainly, the next decade will see massive efforts to use beige and brown fat to ameliorate human metabolic disease.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, adipose organ, thermogenesis, energy expenditure
38
Zhou, Hongyi, Stephen M. Black, Tyler W. Benson, Neal L. Weintraub, and Weiqin Chen. "Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function." Molecular and Cellular Biology 36, no. 15 (May 16, 2016): 2027–38. http://dx.doi.org/10.1128/mcb.01120-15.
Full textAbstract:
Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion ofBscl2in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell-autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.
39
Gharanei, Seley, Kiran Shabir, James E. Brown, Martin O. Weickert, Thomas M. Barber, Ioannis Kyrou, and Harpal S. Randeva. "Regulatory microRNAs in Brown, Brite and White Adipose Tissue." Cells 9, no. 11 (November 16, 2020): 2489. http://dx.doi.org/10.3390/cells9112489.
Full textAbstract:
MicroRNAs (miRNAs) constitute a class of short noncoding RNAs which regulate gene expression by targeting messenger RNA, inducing translational repression and messenger RNA degradation. This regulation of gene expression by miRNAs in adipose tissue (AT) can impact on the regulation of metabolism and energy homeostasis, particularly considering the different types of adipocytes which exist in mammals, i.e., white adipocytes (white AT; WAT), brown adipocytes (brown AT; BAT), and inducible brown adipocytes in WAT (beige or brite or brown-in-white adipocytes). Indeed, an increasing number of miRNAs has been identified to regulate key signaling pathways of adipogenesis in BAT, brite AT, and WAT by acting on transcription factors that promote or inhibit adipocyte differentiation. For example, MiR-328, MiR-378, MiR-30b/c, MiR-455, MiR-32, and MiR-193b-365 activate brown adipogenesis, whereas MiR-34a, MiR-133, MiR-155, and MiR-27b are brown adipogenesis inhibitors. Given that WAT mainly stores energy as lipids, whilst BAT mainly dissipates energy as heat, clarifying the effects of miRNAs in different types of AT has recently attracted significant research interest, aiming to also develop novel miRNA-based therapies against obesity, diabetes, and other obesity-related diseases. Therefore, this review presents an up-to-date comprehensive overview of the role of key regulatory miRNAs in BAT, brite AT, and WAT.
40
Giordano, Antonio, Arianna Smorlesi, Andrea Frontini, Giorgio Barbatelli, and Saverio Cinti. "MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ." European Journal of Endocrinology 170, no. 5 (May 2014): R159—R171. http://dx.doi.org/10.1530/eje-13-0945.
Full textAbstract:
In mammals, adipocytes are lipid-laden cells making up the parenchyma of the multi-depot adipose organ. White adipocytes store lipids for release as free fatty acids during fasting periods; brown adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the pink adipocyte, has recently been characterised in mouse subcutaneous fat depots during pregnancy and lactation. Pink adipocytes are mammary gland alveolar epithelial cells whose role is to produce and secrete milk. Emerging evidence suggests that they derive from the transdifferentiation of subcutaneous white adipocytes. The functional response of the adipose organ to a range of metabolic and environmental challenges highlights its extraordinary plasticity. Cold exposure induces an increase in the ‘brown’ component of the organ to meet the increased thermal demand; in states of positive energy balance, the ‘white’ component expands to store excess nutrients; finally, the ‘pink’ component develops in subcutaneous depots during pregnancy to ensure litter feeding. At the cell level, plasticity is provided not only by stem cell proliferation and differentiation but also, distinctively, by direct transdifferentiation of fully differentiated adipocytes by the stimuli that induce genetic expression reprogramming and through it a change in phenotype and, consequently function. A greater understanding of adipocyte transdifferentiation mechanisms would have the potential to shed light on their biology as well as inspire novel therapeutic strategies against metabolic syndrome (browning) and breast cancer (pinking).
41
Greenhill, Claire. "Engineering brown-like adipocytes." Nature Reviews Endocrinology 16, no. 11 (September 14, 2020): 624–25. http://dx.doi.org/10.1038/s41574-020-00422-9.
Full text
42
Zhao, Qingwen, Zhe Zhang, Weiqiong Rong, Weiwei Jin, Linyu Yan, Wenfang Jin, Yingjiang Xu, Xuan Cui, Qi-Qun Tang, and Dongning Pan. "KMT5c modulates adipocyte thermogenesis by regulatingTrp53expression." Proceedings of the National Academy of Sciences 117, no. 36 (August 24, 2020): 22413–22. http://dx.doi.org/10.1073/pnas.1922548117.
Full textAbstract:
Brown and beige adipocytes harbor the thermogenic capacity to adapt to environmental thermal or nutritional changes. Histone methylation is an essential epigenetic modification involved in the modulation of nonshivering thermogenesis in adipocytes. Here, we describe a molecular network leading by KMT5c, a H4K20 methyltransferase, that regulates adipocyte thermogenesis and systemic energy expenditure. The expression ofKmt5cis dramatically induced by a β3-adrenergic signaling cascade in both brown and beige fat cells. DepletingKmt5cin adipocytes in vivo leads to a decreased expression of thermogenic genes in both brown and subcutaneous (s.c.) fat tissues. These mice are prone to high-fat-diet-induced obesity and develop glucose intolerance. Enhanced transformation related protein 53 (Trp53) expression inKmt5cknockout (KO) mice, that is due to the decreased repressive mark H4K20me3 on its proximal promoter, is responsible for the metabolic phenotypes. Together, these findings reveal the physiological role for KMT5c-mediated H4K20 methylation in the maintenance and activation of the thermogenic program in adipocytes.
43
Phillips, Kevin J. "Beige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone." Biology 8, no. 3 (July 31, 2019): 57. http://dx.doi.org/10.3390/biology8030057.
Full textAbstract:
While it is now understood that the proper expansion of adipose tissue is critically important for metabolic homeostasis, it is also appreciated that adipose tissues perform far more functions than simply maintaining energy balance. Adipose tissue performs endocrine functions, secreting hormones or adipokines that affect the regulation of extra-adipose tissues, and, under certain conditions, can also be major contributors to energy expenditure and the systemic metabolic rate via the activation of thermogenesis. Adipose thermogenesis takes place in brown and beige adipocytes. While brown adipocytes have been relatively well studied, the study of beige adipocytes has only recently become an area of considerable exploration. Numerous suggestions have been made that beige adipocytes can elicit beneficial metabolic effects on body weight, insulin sensitivity, and lipid levels. However, the potential impact of beige adipocyte thermogenesis on systemic metabolism is not yet clear and an understanding of beige adipocyte development and regulation is also limited. This review will highlight our current understanding of beige adipocytes and select factors that have been reported to elicit the development and activation of thermogenesis in beige cells, with a focus on factors that may represent a link between exercise and ‘beiging’, as well as the role that thyroid hormone signaling plays in beige adipocyte regulation.
44
VILLENA, Josep A., Octavi VIÑAS, Teresa MAMPEL, Roser IGLESIAS, Marta GIRALT, and Francesc VILLARROYA. "Regulation of mitochondrial biogenesis in brown adipose tissue: nuclear respiratory factor-2/GA-binding protein is responsible for the transcriptional regulation of the gene for the mitochondrial ATP synthase β subunit." Biochemical Journal 331, no. 1 (April 1, 1998): 121–27. http://dx.doi.org/10.1042/bj3310121.
Full textAbstract:
The regulation of transcription of the gene for the β subunit of the FoF1 ATP synthase (ATPsynβ) in brown adipose tissue has been studied as a model to determine the molecular mechanisms for mitochondrial biogenesis associated with brown adipocyte differentiation. The expression of the ATPsynβ mRNA is induced during the brown adipocyte differentiation that occurs during murine prenatal development or when brown adipocytes differentiate in culture. This induction occurs in parallel with enhanced gene expression for other nuclear and mitochondrially-encoded components of the respiratory chain/oxidative phosphorylation system (OXPHOS). Transient transfection assays indicated that the expression of the ATPsynβ gene promoter is higher in differentiated HIB-1B brown adipocytes than in non-differentiated HIB-1B cells. A major transcriptional regulatory site was identified between nt -306 and -266 in the ATPsynβ promoter. This element has a higher enhancer capacity in differentiated brown adipocyte HIB-1B cells than in non-differentiated cells. Electrophoretic shift analysis indicated that Sp1and nuclear respiratory factor-2/GA-binding protein (NRF2/GABP) were the main nuclear proteins present in brown adipose tissue that bind this site. Double-point mutant analysis indicated a major role for the NRF2/GABP site in the enhancer capacity of this element in brown fat cells. It is proposed that NRF2/GABP plays a pivotal role in the co-ordinated enhancement of OXPHOS gene expression associated with mitochondrial biogenesis in brown adipocyte differentiation.
45
Dufau, Jérémy, Joanne X. Shen, Morgane Couchet, Thais De Castro Barbosa, Niklas Mejhert, Lucas Massier, Elena Griseti, et al. "In vitro and ex vivo models of adipocytes." American Journal of Physiology-Cell Physiology 320, no. 5 (May 1, 2021): C822—C841. http://dx.doi.org/10.1152/ajpcell.00519.2020.
Full textAbstract:
Adipocytes are specialized cells with pleiotropic roles in physiology and pathology. Several types of fat cells with distinct metabolic properties coexist in various anatomically defined fat depots in mammals. White, beige, and brown adipocytes differ in their handling of lipids and thermogenic capacity, promoting differences in size and morphology. Moreover, adipocytes release lipids and proteins with paracrine and endocrine functions. The intrinsic properties of adipocytes pose specific challenges in culture. Mature adipocytes float in suspension culture due to high triacylglycerol content and are fragile. Moreover, a fully differentiated state, notably acquirement of the unilocular lipid droplet of white adipocyte, has so far not been reached in two-dimensional culture. Cultures of mouse and human-differentiated preadipocyte cell lines and primary cells have been established to mimic white, beige, and brown adipocytes. Here, we survey various models of differentiated preadipocyte cells and primary mature adipocyte survival describing main characteristics, culture conditions, advantages, and limitations. An important development is the advent of three-dimensional culture, notably of adipose spheroids that recapitulate in vivo adipocyte function and morphology in fat depots. Challenges for the future include isolation and culture of adipose-derived stem cells from different anatomic location in animal models and humans differing in sex, age, fat mass, and pathophysiological conditions. Further understanding of fat cell physiology and dysfunction will be achieved through genetic manipulation, notably CRISPR-mediated gene editing. Capturing adipocyte heterogeneity at the single-cell level within a single fat depot will be key to understanding diversities in cardiometabolic parameters among lean and obese individuals.
46
Miyajima, Yurina, Kafi N. Ealey, Yasutaka Motomura, Miho Mochizuki, Natsuki Takeno, Motoko Yanagita, Aris N. Economides, Manabu Nakayama, Haruhiko Koseki, and Kazuyo Moro. "Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis." International Immunology 32, no. 6 (March 9, 2020): 407–19. http://dx.doi.org/10.1093/intimm/dxaa013.
Full textAbstract:
Abstract Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.
47
Kiskinis, Evangelos, Lemonia Chatzeli, Edward Curry, Myrsini Kaforou, Andrea Frontini, Saverio Cinti, Giovanni Montana, Malcolm G. Parker, and Mark Christian. "RIP140 Represses the “Brown-in-White” Adipocyte Program Including a Futile Cycle of Triacyclglycerol Breakdown and Synthesis." Molecular Endocrinology 28, no. 3 (March 1, 2014): 344–56. http://dx.doi.org/10.1210/me.2013-1254.
Full textAbstract:
Abstract Receptor-interacting protein 140 (RIP140) is a corepressor of nuclear receptors that is highly expressed in adipose tissues. We investigated the role of RIP140 in conditionally immortal preadipocyte cell lines prepared from white or brown fat depots. In white adipocytes, a large set of brown fat-associated genes was up-regulated in the absence of RIP140. In contrast, a relatively minor role can be ascribed to RIP140 in the control of basal gene expression in differentiated brown adipocytes because significant changes were observed only in Ptgds and Fabp3. The minor role of RIP140 in brown adipocytes correlates with the similar histology and uncoupling protein 1 and CIDEA staining in knockout compared with wild-type brown adipose tissue (BAT). In contrast, RIP140 knockout sc white adipose tissue (WAT) shows increased numbers of multilocular adipocytes with elevated staining for uncoupling protein 1 and CIDEA. Furthermore in a white adipocyte cell line, the markers of BRITE adipocytes, Tbx1, CD137, Tmem26, Cited1, and Epsti1 were repressed in the presence of RIP140 as was Prdm16. Microarray analysis of wild-type and RIP140-knockout white fat revealed elevated expression of genes associated with cold-induced expression or high expression in BAT. A set of genes associated with a futile cycle of triacylglycerol breakdown and resynthesis and functional assays revealed that glycerol kinase and glycerol-3-phosphate dehydrogenase activity as well as [3H]glycerol incorporation were elevated in the absence of RIP140. Thus, RIP140 blocks the BRITE program in WAT, preventing the expression of brown fat genes and inhibiting a triacylglycerol futile cycle, with important implications for energy homeostasis.
48
Colson, Cécilia, Pierre-Louis Batrow, Nadine Gautier, Nathalie Rochet, Gérard Ailhaud, Franck Peiretti, and Ez-Zoubir Amri. "The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes." Cells 9, no. 11 (November 7, 2020): 2433. http://dx.doi.org/10.3390/cells9112433.
Full textAbstract:
Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response.
49
Cunningham, S. A., and D. G. Nicholls. "Induction of functional uncoupling protein in guinea pigs infused with noradrenaline. Studies with isolated brown adipocytes." Biochemical Journal 245, no. 2 (July 15, 1987): 485–91. http://dx.doi.org/10.1042/bj2450485.
Full textAbstract:
Continuous infusion of noradrenaline over the interscapular brown fat of guinea pigs maintained at thermoneutrality (28-32 degrees C) induces changes similar to those after cold-adaptation. (1) Multilocular fat droplets appear within the brown adipocytes. (2) The number of mitochondria per adipocyte and the total number of adipocytes both increase. (3) Noradrenaline addition to isolated adipocytes causes near maximal uncontrolled respiration. (4) The cells become more sensitive to fatty acid-induced uncoupling. (5) The tissue-specific uncoupling protein per mg of mitochondrial protein is increased 5-fold. Specific alpha- and beta-agonists were also chronically infused. (6) Separate infusion of phenylephrine or isoprenaline was not able to stimulate mitochondriogenesis or hyperplasia. (7) Adipocytes from these animals could not be uncoupled by acute noradrenaline. (8) Simultaneous chronic infusion of phenylephrine and isoprenaline reproduced the effects of chronic noradrenaline infusion.
50
Himms-Hagen, J., A. Melnyk, M. C. Zingaretti, E. Ceresi, G. Barbatelli, and S. Cinti. "Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes." American Journal of Physiology-Cell Physiology 279, no. 3 (September 1, 2000): C670—C681. http://dx.doi.org/10.1152/ajpcell.2000.279.3.c670.
Full textAbstract:
Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.