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

Three experiments were carried out to compare plasma lipid and glucose concentrations in genetically lean (LL) and fat (FL) male chickens. The fat birds always displayed lower glycemia than the lean ones, irrespective of the diet (low-fat or fatty) and nutritional state (fed or fasted). Conversely, triglyceridemia was higher in the fat than in the lean line, particularly in the fed condition. This difference was more pronounced in the birds fed on a low-fat diet and became still more marked as they aged. No consistent differences were found between the two lines as to cholesterolemia and non-esterified fatty acid concentrations. Injections of Triton WR 1339 increased triglyceridemia; this effect tended to be more pronounced in the fat birds. The rate of increase of triglyceridemia did not plateau as the dose of Triton increased. The injection of Triton frequently led to convulsions and death. It is concluded that this model of genetic fatness is different from the monogenic models of mammalian obesity since hypertriglyceridemia was not systematic and was not associated with hyperglycemia or hyperinsulinemia.
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PMID:Effects of age and diet on plasma lipid and glucose concentrations in genetically lean or fat chickens. 670 57

Results from experiments on two strains of domestic rabbit show that despite their hopping gait, circadian locomotor rhythms can be successfully measured using running wheels specially designed for large laboratory mammals. Three female rabbits of an English outbred strain were monitored in a 13:11 light:dark (LD) cycle and in constant light (LL), while 12 Dutch-Himalayan rabbits were monitored in a 14:10 LD cycle and constant dark (DD). Much stronger rhythms were observed in the latter strain, which under LD conditions showed individuals with patterns that varied from nocturnal (n = 5), diurnal (n = 4), crepuscular (n = 1), and predominantly arrhythmic (n = 2). In DD, 10 rabbits showed strong free-running rhythms, five with tau (tau) less than 24 h and five longer. The predominantly arrhythmic activity pattern in the remaining two made estimation of tau difficult. Differences in circadian patterns both under LD and DD were unrelated to sex. Results show that locomotor rhythms of the rabbit can be measured using the running wheel, the traditional apparatus of chronobiology. However, the experiments suggest also that the large-bodied breed of rabbits that tend towards obesity, such as the English outbred strain, are relatively inactive and that smaller, more active breeds such as the Dutch-Himalayan may be more suitable for studying circadian rhythmicity if the running wheel is employed.
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PMID:Circadian wheel running activity rhythms in two strains of domestic rabbit. 815 83

Body temperature (Tb) and activity were recorded by telemetry in obese and lean Zucker rats in light-dark (LD), constant dark (DD) and constant light (LL). In LD, obese rats, by comparison with lean rats, exhibited a 2-4-h phase advance and attenuated amplitude of Tb and activity rhythms. These differences persisted on the first day of DD, and thus were not due to differential sensitivity to masking effects of light. In LL, obese and lean rats exhibited similar free-running periods, thus the phase advance in LD was also not due to a short intrinsic period. In LD, obese rats exhibited more diurnal food intake and a reduced LD intake ratio. To assess the role of diurnal feeding in weight gain, one group of obese rats was fed ad libitum, and another fed only at night. Food intake did not differ significantly between groups, but ad libitum fed rats gained 23% more weight (60 g) over 60 days, suggesting that excessive diurnal feeding may contribute adversely to body weight regulation in this animal model of obesity.
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PMID:Circadian rhythms in the Zucker obese rat: assessment and intervention. 963 57

S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P <.05). Treatment with S15261 or S15511 decreased plasma insulin levels in fed rats and prevented the postprandial peak in insulin levels in a meal tolerance test. Y415 had no effect on insulin levels. Troglitazone halved the insulin response to the test meal, but metformin gave no improvement. S15261 decreased the expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase and stimulated the expression of acetyl-CoA carboxylase and acyl-CoA synthase. S15261 also reduced the expression of carnitine palmitoyltransferase I and hydroxymethyl-glutaryl-CoA synthase. S15261, but not troglitazone, reduced the exaggerated contractile response of mesenteric resistance vessels to norepinephrine, and increased the maximal nitric oxide-mediated relaxation. S15261, through S15511, increased insulin sensitivity, decreased insulin levels, and reduced the vasculopathy of the JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.
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PMID:Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat. 1104 15

Diacylglycerol (DG) comprises up to approximately 10% of various edible oils. In the present study, we examined the effects of dietary DG consisting mainly of 1,3-species on body weight, body fat accumulation, and mRNA levels of various genes involved in energy homeostasis in obesity-prone C57BL/6J mice. Five-month feeding with the high triacylglycerol (TG) diet (30% TG + 13% sucrose) resulted in significant increases in body weight, visceral fat accumulation, and circulating insulin and leptin levels compared with mice fed the control diet (5% TG). Compared with mice fed the high TG diet, body weight gain and visceral fat weight were reduced by 70% and 79%, respectively, in those fed the high DG diet (30% DG + 13% sucrose). In addition, circulating leptin and insulin levels were reduced to the respective control levels. Compared with high TG feeding, high DG feeding suppressed the elevation of leptin mRNA expression in adipose tissue, and up-regulated acyl-coenzyme (Co)A oxidase and acyl-CoA synthase mRNA expression in the liver. These results indicate that dietary DG is beneficial for suppression of high fat diet-induced body fat accumulation. Furthermore, it is suggested that structural differences in DG and TG, but not the composition of fatty acid, markedly affect nutritional behavior of lipids. -- Murase, T., T. Mizuno, T. Omachi, K. Onizawa, Y. Komine, H. Kondo, T. Hase, and I. Tokimitsu. Dietary diacylglycerol suppresses high fat and high sucrose diet-induced body fat accumulation in C57BL/6J mice. J. Lipid Res. 2001. 42: 372--378.
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PMID:Dietary diacylglycerol suppresses high fat and high sucrose diet-induced body fat accumulation in C57BL/6J mice. 1125 49

The thiazolidinediones (TZDs) or 'glitazones' are a new class of oral antidiabetic drugs that improve metabolic control in patients with type 2 diabetes through the improvement of insulin sensitivity. TZDs exert their antidiabetic effects through a mechanism that involves activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPAR gamma), a nuclear receptor. TZD-induced activation of PPAR gamma alters the transcription of several genes involved in glucose and lipid metabolism and energy balance, including those that code for lipoprotein lipase, fatty acid transporter protein, adipocyte fatty acid binding protein, fatty acyl-CoA synthase, malic enzyme, glucokinase and the GLUT4 glucose transporter. TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR gamma is predominantly expressed in adipose tissue. It is possible that the effect of TZDs on insulin resistance in muscle and liver is promoted via endocrine signalling from adipocytes. Potential signalling factors include free fatty acids (FFA) (well-known mediators of insulin resistance linked to obesity) or adipocyte-derived tumour necrosis factor-alpha (TNF-alpha), which is overexpressed in obesity and insulin resistance. Although there are still many unknowns about the mechanism of action of TZDs in type 2 diabetes, it is clear that these agents have the potential to benefit the full 'insulin resistance syndrome' associated with the disease. Therefore, TZDs may also have potential benefits on the secondary complications of type 2 diabetes, such as cardiovascular disease.
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PMID:The mode of action of thiazolidinediones. 1192 33

Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces insulin resistance is not understood. By using 3T3-L1 adipocytes and oligonucleotide microarrays, we identified 142 known genes reproducibly upregulated by at least threefold after 4 h and/or 24 h of TNF-alpha treatment, and 78 known genes downregulated by at least twofold after 24 h of TNF-alpha incubation. TNF-alpha-induced genes include transcription factors implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules. Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/enhancer binding protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator-activated receptor gamma were significantly downregulated by TNF-alpha treatment. Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT). Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses. However, absence of NF-kappaB activation abolished suppression of >98% of the genes normally suppressed by TNF-alpha and induction of 60-70% of the genes normally induced by TNF-alpha. Moreover, extensive cell death occurred in IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment. Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance. Further, NF-kappaB is an obligatory mediator of most of these TNF-alpha responses.
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PMID:Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. 1197 27

We measured serum leptin levels in two groupings of wild male baboons, one with access to abundant quantities of food from gardens and garbage dumps near human habitations (Garbage; n = 11) and one without access (No Garbage; n = 10). A Garbage subgroup had high leptin levels (Garbage HL), whereas the rest of the Garbage group had low leptin levels (Garbage LL) similar to those in the No Garbage group. The Garbage HL individuals were obese, with higher mass, body mass index, and leptin to mass ratios; were insulin to resistant, with elevations in serum insulin, glucose, and insulin to glucose ratios; and were hyperlipidemic. This syndrome X-like condition occurred only in the Garbage HL subset. The Garbage LL subset did not differ from the No Garbage individuals in mass, body mass index, leptin to mass ratio, insulin, glucose, or insulin to glucose ratios. The highest cholesterol levels, however, occurred in the Garbage LL individuals, suggesting that susceptibility to hyperlipidemia is distinguishable from susceptibility to obesity and insulin resistance. The differences were not explained by age or social status. These results show that a subgroup of wild baboons is susceptible to developing obesity and insulin resistance and that this susceptibility is not related to age or social rank.
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PMID:Serum leptin levels as a marker for a syndrome X-like condition in wild baboons. 1262 12

The physiologic function of the progressive hyperleptinemia of diet-induced obesity is unknown. However, that lipotoxicity in nonadipose tissues of congenitally unleptinized obese rodents is far greater than in hyperleptinemic diet-induced obesity rodents has suggested an antilipotoxic role. To test this hypothesis, mice with severe lipotoxic cardiomyopathy, induced transgenically by cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene, were made hyperleptinemic by treatment with recombinant adenovirus containing the leptin cDNA. Normoleptinemic control ACS-transgenic mice developed severe dilated cardiomyopathy with thickened left ventricular walls and profound impairment of systolic function on echocardiogram; histologically, there was severe myofiber disorganization and interstitial fibrosis, with intracytoplasmic lipid vacuoles identifiable by electron microscope. By contrast, the hearts of hyperleptinemic ACS-transgenic mice appeared normal, with normal echocardiograms and cardiac triglyceride (TG) contents. Their lower myocardial TG content was ascribed primarily to profound lowering of plasma TG and free fatty acids; free fatty acids were 17% of normal at 8 weeks. Additionally, enhanced myocardial AMP-activated protein kinase phosphorylation may have increased fatty acid oxidation, thereby contributing to the lowering of lipid stores. We conclude that obesity-level hyperleptinemia protects the heart from lipotoxicity.
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PMID:Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice. 1534 5

In vitro studies suggest that the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform catalyzes the initial and rate-controlling step in glycerolipid synthesis and aids in partitioning acyl-CoAs toward triacylglycerol synthesis and away from degradative pathways. To determine whether the absence of mtGPAT1 would increase oxidation of acyl-CoAs and restrict the development of hepatic steatosis, we fed wild type and mtGPAT1-/- mice a diet high in fat and sucrose (HH) for 4 months to induce the development of obesity and a fatty liver. Control mice were fed a diet low in fat and sucrose (LL). With the HH diet, absence of mtGPAT1 resulted in increased partitioning of acyl-CoAs toward oxidative pathways, demonstrated by 60% lower hepatic triacylglycerol content and 2-fold increases in plasma beta-hydroxybutyrate, acylcarnitines, and hepatic mRNA expression of mitochondrial HMG-CoA synthase. Despite the increase in fatty acid oxidation, liver acyl-CoA levels were 3-fold higher in the mtGPAT1-/- mice fed both diets. A lack of difference in CPT1 and FAS mRNA expression between genotypes suggested that the increased acyl-CoA content was not because of increased de novo synthesis, but instead, to an impaired ability to use long-chain acyl-CoAs derived from the diet, even when the dietary fat content was low. Hyperinsulinemia and reduced glucose tolerance on the HH diet was greater in the mtGPAT1-/- mice, which did not suppress the expression of the gluconeogenic genes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. This study demonstrates that mtGPAT1 is essential for normal acyl-CoA metabolism, and that the absence of hepatic mtGPAT1 results in the partitioning of fatty acids away from triacylglycerol synthesis and toward oxidation and ketogenesis.
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PMID:Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs. 1587 74


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