Academic literature on the topic 'Obesity; metabolically abnormal obese; and metabolically normal obese'

Globally, obesity is a severe medical condition that requires novel strategies and acknowledged international agreement to treat illnesses that result in morbidity. Examining the diverse relationships between the different adult obesity phenotypes was the goal of this review. To distinguish between biomarkers, an analysis was conducted on proteins and related genes in each group. There is currently no clear consensus in nomenclature, despite the fact that a number of terminologies are used for classification and characterisation within this disorder. The most important categories that were examined were sarcopenic obesity, metabolically abnormal, normal weight, metabolically healthy obese, and metabolically abnormal obese. These phenotypes don’t specify specific genotypes, epigenetic gene regulation, or inflammatory protein combinations. Numerous other genes have been related to obesity, yet it is still worthwhile to check. Since there are no meaningful biomarkers, the outcomes of those for diagnosis are not very predictive. It is critical to reach agreement on the nomenclature and attributes applied to obesity subtypes. Finding certain molecular biomarkers is also necessary for more accurate detection of obesity subtypes.      

Abstract To clarify the role of obesity in the immune responses, we investigated the relationship between insulin-induced signaling and Toll-like Receptor (TLR)-induced leukocyte cytokine secretion in obese subjects. Peripheral blood samples were collected from metabolically normal (MNO) and metabolically abnormal (MAO) obese subjects and stimulated with TLR agonists. We found elevated IL-1β, IL-10 and decreased IL-6, IFN-γ secretion in both MNO and MAO leukocytes with TLR stimulation when compared with normal leukocytes. Changes in TLR-induced cytokine secretion correlated with biochemical markers including fasting glucose, insulin, homeostasis model assessment (HOMA) index, and body mass index (BMI). Moreover, peripheral blood mononuclear cells (PBMCs) collected from MAO subjects showed enhanced basal Akt / Glycogen Synthase Kinase 3β (GSK3β) phosphorylation which was not further increased by insulin and lipopolysaccharide (LPS). We also found IκB accumulation in PBMCs isolated from normal subjects treated with GSK3β inhibitor lithium chloride. These findings indicate that TLR-induced cytokine secretion is affected by obesity even in subjects who have not reached the criteria of metabolic syndrome. Enhanced leukocyte GSK3β phosphorylation may contribute to aberrant immune response in obese subjects.

Background/Objectives: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status. Methods: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively (p < 0.05). Results: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI > 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88–8.52) for the MANO group and 74.59 (95% CI: 13.29–418.68) for the MAO group compared with the MHNO group. Conclusions: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.

BackgroundGhrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined.ObjectiveWe investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values.DesignA total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR.ResultsIn the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS.ConclusionsA-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.

IntroductionMetabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lipid storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT).Material and methodsGene and protein expression of leptin, adiponectin, and resistin were analyzed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total-, LDL- and HDL-cholesterol levels into metabolically healthy and “at risk” groups.ResultsCompared with normal-weight women, obese women had higher serum leptin levels (P<0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of “at risk” groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (P<0.01), and lower in SAT and VAT (P<0.05) of “at risk” obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin.ConclusionsLow adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean ± sd, 58.0± 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 ± 2.6 mg/min·kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 ± 1.1 mg/min·kg lean body mass). Despite comparable total body fatness between groups (45.2 ± 5.3% vs. 44.8 ± 6.6%; P = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 ± 53 vs. 211 ± 85 cm2; P < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 ± 126 vs. 442 ± 144 cm2; P = NS), total fat mass (38.1 ± 10.6 vs. 40.0 ± 11.8 kg), muscle attenuation (42.2± 2.6 vs. 43.6 ± 4.8 Houndsfield units), and physical activity energy expenditure (1060 ± 323 vs. 1045 ± 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P values ranging between 0.01–0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r2 = 0.35; P < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = −0.107; p = 0.047); adiponectin with BMI (r = −0.217; p = 0.001), insulin (r = −0.415; p = 0.0001), HOMA-IR (r = −0.429; p = 0.0001), and VAT (r = −0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF−21 with insulin (r = −0.337; p= 0.030) and HOMA-IR (r = −0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06–1.81)) and a reduction of adiponectin (OR 0.9 (0.84–0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003–1.011)) and MCP-1 (1.044 (1.008–1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.

Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.

Abstract Background Truncal obesity has long been considered an essential driver of metabolic abnormalities, but it is common for lean individuals with body mass index (BMI) <25 kg/m2 to have one or more metabolic abnormalities. We hypothesized that metabolically unhealthy lean (MUL) individuals have a different distribution of fat compared to their metabolically healthy lean (MHL) counterparts. Methods We performed a retrospective analysis of body composition data obtained from a repository of dual-energy X-ray absorptiometry scans performed during routine clinical practice at a University Bone Clinic. Metabolic data were retrieved from electronic medical records within one calendar year of the index scan. Those with at least 2 components of the metabolic syndrome: blood pressure >130/85 mmHg, triglyceride >150 mg/dL, HDL <50 mg/dL for women and <40 mg/dL for men, fasting plasma glucose >100 mg/dL (or HbA1c >5.7) were considered MUL, while those with 1 component or less were considered MHL. Waist circumference was not considered in this study. Adults with a BMI less than 25 kg/m2 were included in the analysis. Unadjusted and adjusted binary logistic regression were used to analyze the association between metabolic abnormalities and various anthropometric indexes. Results The study population consisted of 119 lean adults with a mean age of 62±14 years and a mean BMI of 22±1.9 kg/m2. Majority of participants were white (88%, n=105) and included postmenopausal women (85%, n=101). A large proportion were of Hispanic ethnicity (41%, n=70). There were 69 (58%) MHL and 50 (42%) MUL individuals. MUL and MHL groups had comparable percentage of total body fat (34±6.6 versus 34±5.6, p=0.360), fat mass index (8.2±1.6 versus 8.1±1.5, p=0.360) and appendicular lean mass (kg/m2) (5.9±0.8 versus 5.8±0.7, p=0.420). However, compared to MHL, MUL subjects had significantly higher visceral adipose tissue (cm2) (87±40 versus 9±29, p=0.004), trunk-to-leg fat ratio (0.89±0.18 versus 0.77±0.13, p<0.001), trunk-to-limb fat ratio (1.00±0.29 versus 0.82±0.18, p<0.001) and android-to-gynoid fat ratio (0.90±0.16 versus 0.81±0.15, p=0.010). After adjusting for age and sex, the odds of being MUL compared to MHL (odds ratio [OR (95% confidence interval (CI))]) increased for every standard deviation increase in visceral adipose tissue (OR=1.75 [1.13-2.73]), trunk-to-leg fat ratio (OR=2.28 [1.30-4.00]), trunk-to-limb fat ratio (OR=2.43 [1.37-4.32]) and android-to-gynoid fat ratio (OR=1.80 [1.07-3.03]). Conclusion Metabolically unhealthy subjects with normal BMI had markedly increased visceral adipose tissue and truncal redistribution of body fat without an increase in total body fat. These findings highlight the importance of using body morphometry measures, rather than total body fat, to assess CVD risk in lean individuals. Our findings suggest that the phenotype of lean individuals with metabolic derangements is not very different from that of obese individuals who have metabolic syndrome as per the National Cholesterol Education Program Adult Treatment Panel-III definition. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

<p>The present study was aimed to find out the frequency of obesity phenotypes and to correlate adipocyte dysfunction with different obesity phenotypes. A total of 1,507 apparently healthy adults attending the outpatient department were grouped into three based on body mass index which were then further categorized into six groups according to metabolically unhealthy or healthy phenotypes by the presence or absence of metabolic syndrome. Of them, metabolically obese normal weight, overweight, healthy obese and unhealthy obese groups were included as obesity phenotypes. Then by purposive sampling, leptin and adiponectin concentration of 184 subjects with different phenotypes were measured to find out the adipocyte dysfunction. Metabolically obese overweight followed by metabolically unhealthy obese were more prevalent i,e., 24.9% and 19.5%. All obesity phenotypes except metabolically obese normal weight were significantly documented with adipocyte dysfunction (p<0.05).</p>

L’obésité est devenue un véritable problème de santé publique. Elle est fréquemment associée à plusieurs anomalies cardiométaboliques telles que l’hypertension artérielle, l’insulinorésistance et les dyslipidémies qui font le lit du diabète de type 2 et des maladies cardiovasculaires. Cependant la fréquence de ces anomalies varie considérablement parmi les sujets obèses faisant de cette maladie chronique une situation clinique très hétérogène. A ce titre un nouveau concept a émergé, impliquant une population de patients sans facteurs de risque apparents, appelé « obèse métaboliquement sain » ou « metabolically healthy obese » (MHO). Des efforts sont en cours pour comprendre les mécanismes sous-jacents à ce phénotype et ses conséquences à long terme. L’objectif principal de cette thèse était d’étudier le lien entre le phénotype MHO et diverses pathologies chroniques connues pour être associées à l’obésité. Les données provenant des cohortes Whitehall II et GAZEL ont été utilisées pour examiner les associations entre le phénotype MHO et la mortalité, les maladies cardiovasculaires, le diabète de type 2 et la dépression. En comparaison aux sujets de poids normal métaboliquement sains, les individus MHO ont un risque accru de mortalité globale et cardiovasculaire, de diabète de type 2 et de maladies cardiovasculaires mais pas de dépression. Comparés aux sujets obèses avec anomalies métaboliques, les individus MHO ont un risque similaire de mortalité et de maladies cardiovasculaires, mais un moindre risque de diabète de type 2 et dépression. Nos résultats suggèrent que l’obésité à profil cardiométabolique normal n’est pas une condition bénigne. Une meilleure compréhension de ce phénotype contribuera à améliorer la décision thérapeutique et aidera peut-être à identifier des cibles thérapeutiques nouvelles<br>Obesity has become a major public health concern. It is frequently associated with several cardiometabolic abnormalities such as hypertension, insulin resistance and dyslipidemia leading to type 2 diabetes and cardiovascular disease. However, the frequency of these abnormalities varies widely among obese subjects, making this chronic condition a very heterogeneous clinical situation. As such a new concept has emerged, involving a population of patients without metabolic risk, called "metabolically healthy obese" (MHO). Intense interest surrounds the MHO phenotype with on-going efforts to understand the mechanisms underlying this phenotype and its long-term consequences. The main objective of this thesis was to study the relationship between the MHO phenotype and various chronic diseases known to be associated with obesity. Data from the Whitehall II and GAZEL cohorts were used to examine associations between this phenotype and mortality, cardiovascular diseases, type 2 diabetes, and depression. Compared to metabolically healthy normal weight subjects, MHO individuals have an increased risk of overall and cardiovascular mortality, type 2 diabetes and cardiovascular diseases, but not depression. Compared to metabolically unhealthy obese subjects, MHO individuals have a similar risk of mortality and cardiovascular disease, but a lower risk of type 2 diabetes, and depression. Our results suggest that obesity with normal cardiometabolic profile is not a benign condition. A better understanding of this phenotype will enhance therapeutic decision making and possibly help to identify new therapeutic targets

This thesis investigates the complexity of the obesity phenotype by characterizing the inflammatory status of Metabolically Healthy Obese (MHO) individuals. More specifically, this work has examined circulating inflammatory markers in MHO individuals and compared it to Lean Healthy (LH) and Metabolically Abnormal Obese (MAO) subjects. Thirty participants (n=10/group) were recruited as part of the Diabetes Risk Assessment (DRA) study, and classified according to adiposity and metabolic status. Despite a similar level of adiposity compared to MAO individuals, MHO subjects presented a more favourable inflammatory profile. Specifically, MHO individuals had levels of hsCRP and IL-6 comparable to LH subjects and lower than MAO subjects. Also, MHO subjects presented similar levels of high molecular weight adiponectin as the MAO group, but PDGF-ββ levels were intermediate to those of the LH and MAO groups. Overall, the distinct inflammatory profile observed in MHO subjects demonstrates the unique status of these individuals, reinforcing that obesity is a complex and heterogeneous phenotype.<br>Public Health Agency of Canada, Ontario Graduate Scholarships, Queen Elizabeth II Graduate Scholarships in Science and Technology, Canada Foundation for Innovation