UMLS:C0028754 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The properties and activity of brown adipose tissue have been investigated in suckling, pre-obese, ob/ob mice in order to determine whether decreased thermogenesis in the tissue precedes the development of obesity in this mutant. At 14 days of age there was no difference between the ob/ob and normal animals in the total amount of interscapular brown adipose tissue, and the DNA content, protein content, and cytochrome oxidase activity of the tissue were similar in the two groups of mice. Respiration rates of brown adipose tissue mitochondria in the presence of albumin were, however, greater in the normal than the ob/ob animals, although after the addition of GDP to recouple the mitochondria there was no difference between the two groups. The mitochondrial membrane potential, measured with [3H]methyltriphenylphosphonium, was less affected by exogenous GDP in ob/ob mice than in normal animals. GDP binding to brown adipose tissue mitochondria, an index of the proton conductance pathway, was much greater in normal than in ob/ob mice at both 10 and 14 days of age; the decreased GDP binding in the mutant animals was found to result from a reduction in the number of binding sites. It is concluded that brown adipose tissue mitochondria of pre-obese ob/ob mice are more tightly coupled than those of normal siblings, and that the activity of the 'thermogenic' proton conductance pathway is lower in the mutant animals. A decrease in thermogenesis in brown adipose tissue is therefore an early event in the development of the ob/ob mouse and precedes the appearance of obesity.
...
PMID:Studies on the activity of brown adipose tissue in suckling, pre-obese, ob/ob mice. 709 44

The objective was to assess the effect of a new, highly selective beta 3-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.
...
PMID:Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. 791 Apr 36

This study compared the effects of aerobic exercise training and chronic administration of the selective beta 2-adrenergic agonist clenbuterol on whole body and skeletal muscle insulin resistance in obese (fa/fa) Zucker rats. Obese rats were randomly assigned to training, clenbuterol, or sedentary control groups. Lean littermates served as a second control group. After 4-5 wk of treatment, an oral glucose tolerance test was performed, followed 1 wk later by hindlimb perfusion, during which time the rates of glucose uptake and 3-O-methyl-D-glucose (3-MG) transport were assessed in the presence of a submaximal (500 microU/ml) insulin concentration. Training resulted in a significant increase in citrate synthase and cytochrome oxidase activity in the recruited muscles. Clenbuterol induced a large increase in muscle mass but provoked a significant decrease in oxidative enzyme activity and beta-adrenergic receptor density. Both treatments increased glucose tolerance and reduced the postglucose insulin response, with the improvements being more pronounced in the clenbuterol group. However, only exercise training improved insulin-stimulated hindlimb muscle glucose uptake (11.37 +/- 0.65, 8.73 +/- 0.77, and 8.27 +/- 0.41 mumol.g-1.h-1 for trained, clenbuterol, and sedentary control groups, respectively) and 3-MG transport. These results suggest that aerobic exercise training attenuated the insulin-resistant condition in the obese Zucker rat by a mechanism other than or in addition to beta 2-adrenergic receptor activation.
...
PMID:Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats. 838 91

C57BL6/J mice with the expression of the mitochondrial uncoupling protein (UCP) gene from the fat-specific aP2 gene promoter were used to study the mechanism by which the aP2-Ucp transgene affects adiposity and reduces high-fat diet induced obesity. In the transgenic mice, UCP synthesized in white fat was inserted into mitochondria, and oxygen uptake by epididymal fat fragments indicated UCP-induced thermogenesis. The respirometry data, UCP content, cytochrome oxidase activity, and tissue morphology suggested functional involution of brown fat. Despite 25- to 50-fold lower mitochondrial cytochrome oxidase activity in white than in brown fat cells, total oxidative capacity in white and brown adipose tissue is comparable. Appearance of novel small cells in the gonadal fat of the transgenic mice was associated with a higher DNA content than that of the nontransgenic mice. The results prove a potential of transgenically altered mitochondria in white fat to modulate adiposity and energy expenditure and suggest the existence of a yet unidentified site-specific link between energy metabolism in adipocytes and cellularity.
...
PMID:Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology. 896 65

Mitochondrial uncoupling protein 1 (UCP1) is a specific marker of multilocular brown adipocytes. Ectopic UCP1 in white fat of aP2-Ucp1 mice mitigates development of obesity by both, increasing energy expenditure and decreasing in situ lipogenesis. In order to further analyse consequences of respiratory uncoupling in white fat, the effects of the ectopic UCP1 on the morphology of adipocytes and biogenesis of mitochondria in these cells were studied. In subcutaneous white fat of both aP2-Ucp1 and young control (5-week-old) mice, numerous multilocular adipocytes were found, while they were absent in adult (7- to 9-month-old) animals. Only unilocular cells were present in epididymal fat of both genotypes. In both fat depots of aP2-Ucp1 mice, the levels of the UCP1 transcript and UCP1 antigen declined during ageing, and they were higher in subcutaneous than in epididymal fat. Under no circumstances could ectopic UCP1 induce the conversion of unilocular into multilocular adipocytes. Presence of ectopic UCP1 in unilocular adipocytes was associated with the elevation of the transcripts for UCP2 and for subunit IV of mitochondrial cytochrome oxidase (COX IV), and increased content of mitochondrial cytochromes. Electron microscopy indicated changes of mitochondrial morphology and increased mitochondrial content due to ectopic UCP1 in unilocular adipocytes. In 3T3-L1 adipocytes, 2,4-dinitrophenol increased the levels of the transcripts for both COX IV and for nuclear respiratory factor-1. Our results indicate that respiratory uncoupling in unilocular adipocytes of white fat is capable of both inducing mitochondrial biogenesis and reducing development of obesity.
...
PMID:Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo. 1178 94

Leptin plays a central role in the regulation of fatty acid homeostasis, promoting lipid storage in adipose tissue and fatty acid oxidation in peripheral tissues. Loss of leptin signaling leads to accumulation of lipids in muscle and loss of insulin sensitivity secondary to obesity. In this study, we examined the direct and indirect effects of leptin signaling on mitochondrial enzymes including those essential for peripheral fatty acid oxidation. We assessed the impact of leptin using the JCR:LA-cp rat, which lacks functional leptin receptors. The activities of marker mitochondrial enzymes citrate synthase (CS) and cytochrome oxidase (COX) were similar between wild-type (+/?) and corpulent (cp/cp) rats. In contrast, several tissues showed variations in the fatty acid oxidizing enzymes carnitine palmitoyltransferase II (CPT II), long-chain acyl-CoA dehydrogenase (LCAD) and 3-hydroxyacyl-CoA dehydrogenase (HOAD). It was not clear if these changes were due to loss of leptin signaling or to insulin insensitivity. Consequently, we examined the effects of leptin on cultured C(2)C(12) and Sol8 cells. Leptin (3 days at 0, 0.2, or 2.0 nM) had no direct effect on the activities of CS, COX, or fatty acid oxidizing enzymes. Leptin treatment did not affect luciferase-based reporter genes under the control of transcription factors involved in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), nuclear respiratory factor-2 (NRF-2)) or fatty acid enzyme expression (peroxisome proliferator-activated receptors (PPARs)). These studies suggest that leptin exerts only indirect effects on mitochondrial gene expression in muscle, possibly arising from insulin resistance.
...
PMID:Leptin and the control of respiratory gene expression in muscle. 1473 84

Since it was first realized that biological energy transduction involves oxygen and ATP, opinions about the amount of ATP made per oxygen consumed have continually evolved. The coupling efficiency is crucial because it constrains mechanistic models of the electron-transport chain and ATP synthase, and underpins the physiology and ecology of how organisms prosper in a thermodynamically hostile environment. Mechanistically, we have a good model of proton pumping by complex III of the electron-transport chain and a reasonable understanding of complex IV and the ATP synthase, but remain ignorant about complex I. Energy transduction is plastic: coupling efficiency can vary. Whether this occurs physiologically by molecular slipping in the proton pumps remains controversial. However, the membrane clearly leaks protons, decreasing the energy funnelled into ATP synthesis. Up to 20% of the basal metabolic rate may be used to drive this basal leak. In addition, UCP1 (uncoupling protein 1) is used in specialized tissues to uncouple oxidative phosphorylation, causing adaptive thermogenesis. Other UCPs can also uncouple, but are tightly regulated; they may function to decrease coupling efficiency and so attenuate mitochondrial radical production. UCPs may also integrate inputs from different fuels in pancreatic beta-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes.
...
PMID:The efficiency and plasticity of mitochondrial energy transduction. 1624 6

A reduced brown adipose phenotype in white adipose tissue (WAT) may contribute to obesity and type 2 diabetes in humans. Retinoic acid, the carboxylic form of vitamin A, triggers in rodents a reduction of body weight and adiposity and an increased expression of uncoupling proteins in brown adipose tissue and skeletal muscle. In this study, we investigated possible remodeling effects of all-trans retinoic acid (ATRA) in WAT depots. Changes in the expression of genes related to thermogenesis and fatty acid oxidation and levels of phosphorylated retinoblastoma protein were analyzed in WAT depots of adult NMRI male mice acutely injected with ATRA or vehicle, together with biometric and blood parameters. Body fat loss after ATRA treatment was unaccompanied by any increase in circulating nonesterified fatty acids or ketone bodies and accompanied by increased rectal temperature. The treatment triggered an up-regulation of the mRNA levels of uncoupling proteins 1 and 2, peroxisome proliferator-activated receptor gamma coactivator-1alpha, peroxisome proliferator-activated receptor alpha, muscle- and liver-type carnitine palmitoyltransferase 1, and subunit II of cytochrome oxidase in different WAT depots. Levels of phosphorylated retinoblastoma protein in WAT depots were increased after ATRA treatment. Adipocyte size was reduced, and the number of multilocular adipocytes was increased in inguinal WAT of ATRA-treated mice. The results indicate that ATRA favors the acquisition of brown adipose tissue-like properties in WAT. Understanding the mechanisms and effectors involved in the remodeling of WAT can contribute to new avenues of prevention and treatment of obesity and type 2 diabetes.
...
PMID:Remodeling of white adipose tissue after retinoic acid administration in mice. 1684 May 43

Ciliary neurotrophic factor (CNTF) can lead to weight loss by up-regulating energy metabolism and the expression of UCP-1 in mitochondria. To investigate the up-stream regulators of the expression of UCP-1, recombinant human CNTF (rhCNTF) (0.1, 0.3, 0.9 mg/kg/day s.c.) administered to KK-Ay mice for 30 days resulting in reductions in body weight and perirenal fat mass. In brown adipose tissues, the gene expressions of nuclear respiratory factor (NRF)-1, mitochondrial transcription factor A (TFam) and uncoupling protein (UCP)-1 were found up-regulated by rhCNTF. To the best of our knowledge, these effects represent new insights on the mechanisms of action of weight loss by rhCNTF. In addition, we also found that rhCNTF increased the activity of mitochondrial complex IV. The stimulation of NRF-1, TFam, UCP-1 and the enhanced activity of mitochondrial complex IV may be associated with remedying obesity. The result indicates that rhCNTF can enhance the expressions of NRF-1 and TFam, both of which can up-regulate the expression of UCP-1.
...
PMID:Recombinant human ciliary neurotrophic factor reduces weight partly by regulating nuclear respiratory factor 1 and mitochondrial transcription factor A. 1739 29

Resveratrol is a naturally occurring polyphenol known to affect energy metabolism and insulin sensitivity in mice and lipogenic gene expression in adipocytes. Here, we sought to get further insight into the impact of resveratrol on adipocyte biology by studying its effects on oxidative metabolism and the expression of the insulin resistance-related adipokines resistin and Retinol-Binding Protein 4 (RBP4) in mature adipocytes. Effects were assessed in 3T3-L1 adipocytes and in adipocytes derived from primary mouse embryonic fibroblasts (MEF). Besides reducing triacylglycerol content and the mRNA levels of lipogenic genes, resveratrol treatment resulted in both models in increased mRNA levels of carnitine palmitoyltransferase 1 (a rate-limiting enzyme in mitochondrial fatty acid oxidation), reduced mRNA levels of receptor interacting protein 140 (a suppressor of oxidative metabolism), and signs of enhanced flux through the fatty acid beta-oxidation pathway. In primary MEF-derived adipocytes, the treatment also increased mitochondrial DNA content and the mRNA levels of subunit II of cytochrome oxidase (a component of the mitochondrial respiratory chain) and of uncoupling protein 1. Expression of resistin and RBP4 was reduced in both adipocyte models following resveratrol treatment. The results indicate that resveratrol directly acts in mature white adipocytes to favor a remodeling toward increased oxidative capacity and reduced lipogenesis, while down-regulating two putative insulin resistance factors. These results constitute novel insights into resveratrol action in adipocytes that add to the potential of this food phytochemical and its synthetic analogues for the control of obesity and related metabolic disorders.
...
PMID:Resveratrol enhances fatty acid oxidation capacity and reduces resistin and Retinol-Binding Protein 4 expression in white adipocytes. 2110 18

<< Previous 1 2 3 4 5 Next >>