Academic literature on the topic 'Rat diet/iron uptake study'

Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (β-hydroxybutyrate, acetoacetate, and acetone) produced in liver mitochondria from fatty acid β-oxidation. Although moderately raised blood ketones produced on a very high fat ketogenic diet have important clinical effects on the brain, including reducing seizures, ketone metabolism by the brain is still poorly understood. The aim of the present work was to assess brain uptake of carbon-11-labeled acetoacetate (11C-acetoacetate) by positron emission tomography (PET) imaging in the intact, living rat. To vary plasma ketones, we used three dietary conditions: high carbohydrate control diet (low plasma ketones), fat-rich ketogenic diet (raised plasma ketones), and 48-h fasting (raised plasma ketones). 11C-acetoacetate metabolism was measured in the brain, heart, and tissue in the mouth area. Using 11C-acetoacetate and small animal PET imaging, we have noninvasively quantified an approximately seven- to eightfold enhanced brain uptake of ketones on a ketogenic diet or during fasting. This opens up an opportunity to study brain ketone metabolism in humans.

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.

Homozygous Belgrade rats have an inherited hypochromic, microcytic anemia that is due to impaired iron transport into immature erythrocytes. There is also evidence for abnormal iron transport in other tissues such as the intestine. This study was aimed at investigating the intestinal defect in rats that had been fed diets for 12 days that are normal, low, or high in iron. The duodenal uptake, transfer, and absorption of Fe(III)-nitrilotriacetate and Fe(II)-ascorbate were studied using in vivo tied-off gut sacs in genetically normal rats and in heterozygous or homozygous Belgrade rats. In normal and heterozygous Belgrade rats, the handling of Fe(III) and Fe(II) was similar; uptake, transfer, and absorption of Fe(III) and Fe(II) changed inversely with the iron content of the diet. In contrast, in homozygous Belgrade rats the uptake of both Fe(III) and Fe(II) was markedly reduced and absorption of Fe(III) did not change when animals were fed an iron-deficient diet. Since absorption of Fe(II) was similar to Fe(III), there is no evidence that the defect in iron absorption is due to failure of a mechanism for reduction of Fe(III). The lowered uptake of Fe(III) and Fe(II) in homozygous Belgrade rats probably involves a defective iron carrier associated with the microvillous membrane of the duodenum.

The effect of hypoxic exposure on in vitro duodenal Fe uptake kinetics was studied in tissue fragments from rats that were fed or fasted overnight before study. Hypoxic exposure was for 3 d at 0·5 atm and fasting was for the last 18-24 h before Fe uptake determinations. The non-permeable Fe2+ chelator 3-(2-pyridyl)-5,6-bis-(4-phenyl-sulphonic acid)-l,2,4-triazine (ferrozine), and medium deoxygenation inhibited uptake in all experimental groups. Ferrozine sensitivity and mucosal Fe3+ reductase activity were greatest in hypoxic animals. Fe uptake was inhibited by membrane depolarization only after fasting or hypoxic exposure of the rats. The data demonstrated that Fe uptake by rat duodenal fragments involves at least two mechanisms: a membrane-potentialindependent mechanism which is not responsive to hypoxia and a second mechanism, induced by fasting or hypoxia, which is inhibited by membrane depolarization. Uptake is partially dependent on reduction of Fe3+ to Fe2+ and this is primarily associated with the second mechanism for uptake. These properties have been reported also in mouse and human Fe uptake, suggesting that the rat is a useful model for the study of basic mechanisms of Fe absorption

Anemia can be induced by dietary iron deficiency, as well as by hemorrhagia. It may also be associated with changes in lipid metabolism. However, no global analysis detailing the consequences of iron deficiency in the liver has yet been conducted. Since the liver is a metabolically important organ and also a major iron-storing organ, we performed a comprehensive transcriptome analysis to determine the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet, ∼3 ppm iron, ad libitum for 16 days. These rats were compared with similar rats pair-fed a control diet with a normal iron level, 48 ppm iron. The 16-day iron-deficient diet apparently induced anemia. On day 17, the rats were killed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 upregulated and 500 downregulated probe sets that characterized the iron-deficient diet group. In the upregulated probe sets, genes involved in cholesterol, amino acid, and glucose metabolism were significantly enriched, while genes related to lipid metabolism were significantly enriched in the downregulated probe sets. We also found that genes for caspases 3 and 12, which mediate endoplasmic reticulum (ER)-specific apoptosis, were upregulated in the iron-deficient group. Combined, these results suggest that iron deficiency exerts various influences, not only on nutrient metabolism but also on apoptosis, as a consequence of ER stress in the liver.

The iron-binding protein lactoferrin (Lf) present in blood is metabolized by the liver. Isolated rat hepatocytes vigorously endocytose bovine Lf via recycling Ca2(+)-dependent binding sites, but the uptake of iron from Lf by hepatocytes has not been examined. In this study, isolated rat hepatocytes were incubated with radiolabelled bovine Lf (125I-Lf, 59Fe-Lf or 125I-59Fe-Lf) at 37 degrees C, then washed at 4 degrees C in the presence of dextran sulphate with either Ca2+ or EGTA to distinguish between total bound and internal radioactivity respectively. Cells internalized 125I-Lf protein and Lf-bound 59Fe at maximal endocytic rates of 1700 and 480 mol.cell-1.s-1 respectively. When Lf was normalized for 59Fe content, these endocytic rates were equivalent and reflected an uptake potential of at least 3400 mol of iron.cell-1.s-1. Cells prebound with 125I-59Fe-Lf to Ca2+(-)dependent sites at 4 degrees C internalized more than 80% of both 125I-Lf protein and Lf-bound 59Fe approx. 6 min after warming to 37 degrees C at similar rates (125I-Lf: k(in) = 0.276 min-1, 59Fe: k(in) = 0.303 min-1). Within 4 h at 37 degrees C, cells had released 25% or less internalized Lf protein in the form of acid-soluble 125I-by-products but retained all the Lf-delivered 59Fe. Hyperosmotic disruption of clathrin-dependent endocytosis blocked the uptake of 125I-Lf and Lf-bound 59Fe. Incubation of cells with 125I-59Fe-Lf and a 100 molar excess of diferric transferrin reduced slightly the endocytosis of 125I-Lf protein and 59Fe accumulation. Treatment of cells with the ferric chelator desferrioxamine did not alter uptake of 125I-Lf protein or Lf-bound 59Fe, but the ferrous chelator bathophenanthroline disulphonate slightly elevated endocytosis of 125I-Lf protein and Lf-bound 59Fe. These findings indicate that Lf does not release its bound iron before endocytosis. It was concluded from this study that hepatocytes take up iron from Lf at high rates by a process that requires endocytosis of Lf-iron complexes.

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0–12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.

ABSTRACT Introduction With growing awareness of the link between diet and health and the problem of obesity, public concern over sugar levels in the diet is forcing a worldwide trend toward cutting down on sugar by using artificial sweeteners (AS). Aim To study the effect of increasing concentrations of sucralose (an AS) on glucose uptake in rat L6 myotubes. Materials and methods The L6 cell line from American type cell culture (ATCC) was grown in Dulbecco's Modified Eagle's Medium (DMEM) and differentiated into myotubes. The wells were exposed to either 0, 1 nM, 1 μM, or 1 mM of sucralose alone or with 10 nM insulin for 24 hours. Glucose uptake was studied after this period. Results Significant decrease was seen between the insulin-stimulated basal glucose uptake and insulin-stimulated glucose uptake across all the concentrations of sucralose treatment. Conclusion Increased concentration of sucralose appears to decrease glucose uptake even on insulin stimulation. Clinical significance It may not be beneficial to use sucralose in certain groups of people who have insulin resistance or are prone to it. How to cite this article Prakash SN, Shanthakumari J, Devanath A. Effect of Sucralose on Glucose Uptake in Rat L6 Myotubes. Indian J Med Biochem 2017;21(2):162-165.

Weanling male Wistar rats were fed for 28 d on a semi-synthetic diet containing normal (38 μg/g) or low (9 μg/g) levels of iron. They were given water or tea infusion (20 g leaves/I water) to drink. Two further groups were given a normal- or low-Fe diet containing added tea leaves (20 g/kg diet). At the end of the study period, all rats given the low-Fe diet were severely anaemic, as assessed by haemoglobin, packed cell volume and liver Fe. Those given tea or the diet with added tea leaves showed a greater degree of Fe depletion. The blood and liver aluminium levels were not increased as a result of consuming tea or tea leaves, despite the higher Al intakes. Fe deficiencyper sehad no effect on Al absorption or retention from tea. It was concluded that the Al in tea was very poorly absorbed but that tea, either in the form of an infusion or as tea leaves, had an adverse effect on Fe status

Many research centres have developed various animal models with Iron Deficiency Anaemia (IDA) by using iron deficient feeds as well as different chemicals. Model for iron deficiency anaemia (IDA) in rats has been created by the use of iron elimination from diet components as much as possible. The present study elaborates and concludes the development of IDA rat model by investigating different parameters like body weight, haematological indices, peripheral smear, immunoassay studies and histopathological studies using commercially available iron deficient diet. 12 Wistar albino female rats weighing 180-200 gm were selected with normal haemoglobin range of 12 - 15 g/dL purchased from Bombay Veterinary College, Parel and divided into two groups – Control (3 no. of rats) and Test (9 no. of rats). The test group was fed with iron deficient diet (VRK Nutritional Solutions) whereas control group was fed with standard diet. The time duration of the study was 5 weeks (35 days) and 6 weeks (42 days). Retro orbital blood for both control and treated was drawn at both time intervals so as to analyse haematological and immunoassay studies. Peripheral smear staining was carried out to observe the gross morphology of RBCs for iron deficient and control rats. The body weights were recorded before and after treatment and statistical significance was calculated. Post exposure rats were dissected and organs like heart, kidney, liver, lungs and spleen were collected for histopathological analysis. Our results showed decreased levels of hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), reticulocyte count, serum iron (SI), serum ferritin (SF) and an increase in total iron binding capacity (TIBC). in IDA animals exposed to 42 days of iron deficient diet. Significant difference (p<0.5) was observed in body weights of rats when compared with the data before and after treatment. The peripheral smear has indicated microcytic hypochromic RBCs in test group confirming development of IDA model. The histopathological results revealed the abnormality at cellular level like congestion of blood vessels in heart, congestion and centrilobular hepatocyte with inflammatory cell infiltration in liver, perivasculitis in lungs and decrease in white pulp in spleen whereas kidney were found normal. Our results clearly demonstrate iron deficient rat model when administered with IDA feed. This model can be used for estimation of efficiency of new food products and food supplements enriched with iron.

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including oxygen transport, DNA synthesis, and electron transport. However, iron concentrations in body tissues must be tightly regulated because excessive iron leads to tissue damage, as a result of formation of free radicals. In mammals since no controlled means of eliminating unwanted iron has evolved, body iron balance is maintained by alterations in dietary iron intake. This occurs in the duodenum where most dietary iron is absorbed. Absorption involves at least two steps, uptake of iron from the intestinal lumen and then its transport into the body, processes that occur at the apical and basal membranes of enterocytes, respectively. In chapter one of this thesis the background information relevant to iron absorption is described. Despite numerous studies, the role of these proteins in iron absorption remains unclear, partly because many studies have reported them in non-enterocyte cell lines where the expression of the proteins involved in iron absorption is unlikely and therefore the physiological significance of the findings uncertain. Therefore, the study of iron absorption would value from additional cell lines of intestinal origin being used, preferably derived from a species used to comprehensively study this process in vivo, namely the rat. Validation of such a model would enable comparisons to be made from a molecular level to its relevance in the whole organism. In chapter 3 of this thesis, the rat intestinal cell line 6 (IEC-6) was examined as a model of intestinal iron transport. IEC-6 cells expressed many of the proteins involved in iron absorption, but not the ferrireductase Dcytb, sucrase or αvβ3 integrin. In addition, in IEC-6 cells the expression of the apical transporter divalent metal transporter 1 (DMT1), the iron storage protein ferritin, the uptake of Fe(II) and Fe(III) were regulated by cellular iron stores as is seen in vivo. This suggests that IEC-6 cells are of a lower villus enterocyte phenotype. Presented in chapter 4 is the study of the uptake of iron from Fe(II):ascorbate and Fe(III):citrate by IEC-6 cells in the presence of a blocking antibody to the putative basolateral transporter ferroportin1 and of colchicine and vinblastine, different pHs, and over-expression of DMT1. It was shown that optimal Fe(II) uptake required a low extracellular pH and was dependent on DMT1. Uptake of Fe(III) functioned optimally at a neutral pH, did not require surface ferrireduction, and was increased during over-expression of DMT1. These observations suggest that intravesicular ferrireduction takes place before transport of Fe(II) to the cytoplasm by DMT1. This pathway was not blocked by a functional antibody against αvβ3 integrin but was inhibited by competition with unlabeled iron citrate or citrate alone. Surprisingly, a functional antibody against ferroportin1 had no effect on efflux but significantly reduced (p<0.05) uptake of Fe(II) by 40-50% and Fe(III) by 90%, indicating two separate pathways for the uptake of iron from Fe(II)-ascorbate and from Fe(III)-citrate in IEC-6 cells. Presented in chapter 5 is the development and validation of a technique for the removal of freshly isolated enterocytes from the rat duodenum and their use to study iron transport processes that enabled comparisons to be made between these cells, IEC-6 cells and the human enterocyte cell line Caco-2 cells. In chapter 6 a blocking antibody to ferroportin1 was shown to inhibit uptake of Fe(II) but not release of iron in freshly isolated duodenal enterocytes from rats and Caco-2 cells supporting the findings obtained with IEC-6 cells described in chapter 4. Fe(II) uptake was reduced only when the antibody was in contact with the apical membrane indicating its expression at the microvillus membrane. Confirming this, ferroportin1 was shown along the microvillus membrane of Caco-2 cells, in enriched microvillus membrane preparations and in enterocytes of duodenum tissue of rats where it co-localised with lactase. The significant findings to emerge from this thesis are that the IEC-6 cell is a valid model to study iron absorption producing results consistent with those found in freshly isolated enterocytes and in human enterocyte-like cells. In particular, ferroportin1 functions in the uptake of iron at the apical membrane possibly by modulating surface binding of Fe(II) to DMT1 or the activity of DMT1. In addition to this in Fe(II) uptake from Fe(III) ferroportin1 may also affect the number of Fe(III): citrate binding sites. Preliminary studies further characterizing the function of ferroportin1 at the apical membrane and at intracellular sites of IEC-6 cells along with integration of these data are discussed in chapter 7.