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

Ingestion of nutrients increases energy expenditure above basal metabolic rate. Thermogenesis of carbohydrate comprises two distinct components: an obligatory component, which corresponds to the energy cost of carbohydrate absorption, processing, and storage; and a facultative component, which appears to be related with a carbohydrate-induced stimulation of the sympathetic nervous system, and can be inhibited by beta-adrenergic antagonists. Fructose ingestion induces a greater thermogenesis than does glucose. This can be explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in obligatory thermogenesis. Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. These individuals in contrast display a normal thermogenesis after ingestion of fructose. This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin. This observation indicates that insulin resistance is likely to play an important role in the decreased glucose-induced thermogenesis of these individuals.
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PMID:Fructose and dietary thermogenesis. 821 8

This study was conducted to contribute to the improvement of occupational health surveillance. The subjects of the study were 461 young male workers born between April 1959 to March 1969, who worked at two plants in Tokyo, and who do not usually undergo examination of blood lipid levels at a routine health check-up program. The screening procedure was mainly based on the second report of the National Cholesterol Education Program Expert Panel (Adult Treatment Panel, ATP II). The proportion of the subjects with low HDL-cholesterol level (< 35 mg/dl) was 5.2% for workers in their late twenties (W20) and 8.4% for those in their early thirties (W30). For high LDL-cholesterol (130+ mg/dl), the proportion (underestimated due to non-fasting blood collection) was 7.2% for W20 and 13.5% for W30, and the difference was statistically significant (p < 0.05). Among subjects with low HDL, the proportion of subjects with total cholesterol (TC) being < 200 mg/dl was 94% (15/16) for W20 and 54% (7/13) for W30. This implies that it is difficult to detect subjects with low HDL from values for TC only especially among W20. Hence it is useful to examine HDL in combination with TC. Among subjects with TC being 200-239 mg/dl, the proportion (underestimated) of the subjects with high LDL was 40% for W20 and 26% for W30, and ATP II procedure would fail to incorporate most of them into a treatment program. Thus, accurate estimation of LDL is necessary for subjects with TC being 200+ mg/dl. Relationships of high HDL (60+ mg/dl) to exercise as well as low HDL to obesity (p < 0.05) were found among both age groups. The high prevalence of LDL and HDL abnormality found among the study subjects would imply that it is necessary to initiate evaluation of hyperlipidemia at younger ages and also ATP II procedure needs to be modified for proper surveillance.
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PMID:[Surveillance of hyperlipidemia among young adults in an occupational setting]. 852 41

The brain contains neurons which alter their firing rates when ambient glucose concentrations change. An ATP-sensitive K+ (Katp) channel on these neurons closes and increases cell firing when ATP is produced by intracellular glucose metabolism. Binding of the antidiabetic sulfonylurea drugs to a site linked to this channel has a similar effect. Here rats with a propensity to develop diet-induced obesity (DIO) or to be diet-resistant (DR) when fed a diet moderately high in fat, energy and sucrose (HE diet) had low and high affinity sulfonylurea binding assessed autoradiographically with [3H]glyburide in the presence or absence of Gpp(NH)p. Before HE diet exposure, chow-fed DIO- and DR-prone rats were separated by their high vs. low 24 h urine NE levels. In DR-prone rats, low affinity [3H]glyburide binding sites comprised up to 45% of total binding with highest concentrations in the hypothalamus and amygdala. But DIO-prone rats had few or no low affinity binding sites throughout the forebrain. High affinity [3H]glyburide binding was similar between phenotypes. When rats developed DIO after 3 months on HE diet, their low affinity binding increased slightly. DR rats fed the HE diet gained the same amount of weight as chow-fed controls but their low affinity binding sites were reduced to DIO levels and both were significantly lower than chow-fed controls. By contrast, high affinity [3H]glyburide binding was increased in DR rats throughout the forebrain so that it significantly exceeded that in both DIO and chow-fed control rats. These studies demonstrate a significant population of low affinity sulfonylurea binding sites throughout the forebrain which, along with high affinity sites, are regulated as a function of both weight gain phenotype and diet composition.
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PMID:Differential effects of diet and obesity on high and low affinity sulfonylurea binding sites in the rat brain. 895 50

In the genetic mutant mouse models ob/ob or db/db, leptin deficiency or resistance, respectively, results in severe obesity and the development of a syndrome resembling NIDDM. One of the earliest manifestations in these mutant mice is hyperinsulinemia, suggesting that leptin may normally directly suppress the secretion of insulin. Here, we show that pancreatic islets express a long (signal-transducing) form of leptin-receptor mRNA and that beta-cells bind a fluorescent derivative of leptin (Cy3-leptin). The expression of leptin receptors on insulin-secreting beta-cells was also visualized utilizing antisera generated against an extracellular epitope of the receptor. A functional role for the beta-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice. Furthermore, leptin produced a marked lowering of [Ca2+]i in ob/ob beta-cells, which was accompanied by cellular hyperpolarization and increased membrane conductance. Cell-attached patch measurements of ob/ob beta-cells demonstrated that leptin activated ATP-sensitive potassium channels (K(ATP)) by increasing the open channel probability, while exerting no effect on mean open time. These effects were reversed by the sulfonylurea tolbutamide, a specific inhibitor of K(ATP). Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM.
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PMID:Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. 916 85

Hyperinsulinaemia in the fasting state and a blunted insulin secretory response to acute glucose stimulation are commonly observed in obesity associated non-insulin-dependent diabetes mellitus. Hyperlipidaemia is a hallmark of obesity and may play a role in the pathogenesis of this beta-cell dysfunction because glucose metabolism in pancreatic beta cells may be altered by the increased lipid load. We tested this hypothesis by assessing the chronic effect of oleic acid on glucose metabolism and its relationship with glucose-induced insulin release in beta HC9 cells in tissue culture. Our results show: (1) A 4-day treatment with oleic acid caused an enhancement of insulin release at 0-5 mmol/l glucose concentrations while a significant decrease in insulin release occurred when the glucose level was greater than 15 nmol/l; (2) Hexokinase activity was increased and a corresponding left shift of the dose-dependency curve of glucose usage was observed associated with inhibition of glucose oxidation in oleic acid treated beta HC9 cells, yet the presumed glucose-related ATP generation did not parallel the change in insulin release due to glucose; (3) The rate of cellular respiration was markedly increased in oleic acid treated beta HC9 cells both in the absence of glucose and at all glucose concentrations tested. This enhanced oxidative metabolism may explain the increased insulin release at a low glucose level but is clearly dissociated from the blunted insulin secretion at high glucose concentrations. We conclude that a reduction of oxidative metabolism in pancreatic beta cells is unlikely to be the cause of the dramatic effect that high levels of non-esterified fatty acids have on glucose-induced insulin release.
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PMID:Chronic effect of fatty acids on insulin release is not through the alteration of glucose metabolism in a pancreatic beta-cell line (beta HC9). 930 Feb 38

Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis. The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis. We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue. Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein. UCP3 RNA levels are regulated by hormonal and dietary manipulations. In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation. In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased 6-fold in hyperthyroid rats. Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis. UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation. The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity.
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PMID:Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. 930 58

Tumor necrosis factor (TNF)-alpha may play a role in the insulin resistance of obesity and NIDDM. Troglitazone is a new orally active hypoglycemic agent that has been shown to ameliorate insulin resistance and hyperinsulinemia in both diabetic animal models and NIDDM subjects. To determine whether this drug could prevent the development of TNF-alpha-induced insulin resistance, glucose turnover was assessed in rats infused with cytokine and pretreated with troglitazone. Normal male Sprague-Dawley rats were fed normal powdered food with or without troglitazone as a food admixture (0.2%). After approximately 10 days, rats were infused with TNF-alpha for 4-5 days, producing a plasma concentration of 632 +/- 30 pg/ml. In vivo insulin action was measured by the euglycemic-hyperinsulinemic clamp technique at a submaximal (24 micromol x kg[-1] x min[-1]) and maximal insulin infusion rate (240 micromol x kg[-1] x min[-1]). TNF-alpha infusion resulted in a pronounced reduction in submaximal insulin-stimulated glucose disposal rate (GDR) (97 +/- 10 vs. 141 +/- 4 micromol x kg[-1] x min[-1], P < 0.05), maximal GDR (175 +/- 8 vs. 267 +/- 6 micromol x kg[-1] x min[-1], P < 0.01), and in insulin receptor-tyrosine kinase activity (IR-TKA) (248 +/- 39 vs. 406 +/- 32 fmol ATP/fmol IR, P < 0.05). It also led to a marked increase in basal insulin (90 +/- 24 vs. 48 +/- 6 micromol/l, P < 0.05) and free fatty acid (FFA) concentration (2.56 +/- 0.76 vs. 0.87 +/- 0.13 mmol/l, P < 0.01). Troglitazone treatment completely prevented the TNF-alpha-induced decline in submaximal GDR (133 +/- 16 vs. 141 +/- 4 micromol x kg[-1] x min[-1], NS) and maximal GDR (271 +/- 19 vs. 267 +/- 6 micromol x kg[-1] x min[-1], NS). The hyperlipidemia was partially corrected by troglitazone (1.53 +/- 0.28 vs. 0.87 +/- 0.13 mmol/l, P < 0.05), while IR-TKA and insulin concentration remained unaffected by the drug. Troglitazone restores insulin action possibly by lowering the FFA concentration of the blood and/or by stimulating glucose uptake at an intracellular point distal to insulin receptor autophosphorylation in muscle. If TNF-alpha plays a role in the development of the obesity/NIDDM syndrome, troglitazone may prove useful in its treatment.
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PMID:TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. 935 12

Leptin, the protein encoded by the obese (ob) gene, is secreted from adipose tissue and is thought to act in the central nervous system to regulate food intake and body weight. It has been proposed that leptin acts in the hypothalamus, the main control centre for satiety and energy expenditure. Mutations in leptin or the receptor isoform (Ob-R[L]) present in hypothalamic neurons result in profound obesity and symptoms of non-insulin-dependent diabetes. Here we show that leptin hyperpolarizes glucose-receptive hypothalamic neurons of lean Sprague-Dawley and Zucker rats, but is ineffective on neurons of obese Zucker (fa/fa) rats. This hyperpolarization is due to the activation of a potassium current, and is not easily recovered on removal of leptin, but is reversed by applying the sulphonylurea, tolbutamide. Single-channel recordings demonstrate that leptin activates an ATP-sensitive potassium (K[ATP]) channel. Our data indicate that the K(ATP) channel may function as the molecular end-point of the pathway following leptin activation of the Ob-R(L) receptor in hypothalamic neurons.
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PMID:Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. 939 3

Nutritional obesity induced by the ingestion of hyperlipidic diet implies a high consume of lipids, which might be involved in oxygen metabolism. Double bound, in the fatty-acid molecules are a vulnerable point to undergo oxidation reactions-generating lipid peroxidation, that are potentially toxic and can produce serious cell injury (alteration in cell permeability and prostaglandins...). To prevent this oxidative injury the aerobic organisms have intracellular mechanisms of defense, the antioxidant systems, that may be classified as enzymatic and nonenzymatic. Vitamin C belongs to the second group and acts as scavenger of free radicals and other species. The purpose of this study was to evaluate the oxygen metabolism in isolated hepatocytes of rats which obesity has been reached by the ingestion of an hyperenergetic olive-oil rich controlled liquid diet and evaluate the effect of ascorbic acid. Cellular oxidative injury in isolated hepatocytes was induced through a lipid peroxidative and cytotoxic molecule tert-butyl-hydroperoxide (t-BOOH). Results show higher levels of lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) production in obese rats as compared with controls. Otherwise, when these groups are supplemented with ascorbic acid these changes decrease significantly. ATP levels decrease in hepatocytes of obese rats incubated in the presence of 1 mM tert-butylhydroperoxide. While it is maintained in ascorbic acid supplemented animals. GSH values were lower in hepatocytes from obese and control rats, incubated with tert-butyl-hydroperoxide. Supplementation with ascorbic acid also maintained GSH levels thus indicating that ascorbic acid is acting as an efficient antioxidant.
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PMID:[Oxygen metabolism in isolated rat hepatocytes in obesity. Influence of vitamin C]. 941 88

Select brain neurons increase their firing rate when ambient glucose levels rise, possibly via a neuronal ATP-sensitive K+ (KATP) channel and its associated sulfonylurea receptor (SUR). We used receptor autoradiographic binding of 20 nM [3H]glyburide (in the presence or absence of Gpp(NH)p which blocks binding to low-affinity sites) to assess the in vivo and in vitro effects of altering glucose availability upon high- and low-affinity binding to brain SUR. Since the brain's ability to monitor and regulate glucose metabolism is critical to maintenance of energy balance, testing was done in chow-fed male Sprague-Dawley rats which had an underlying predisposition to develop either diet-induced obesity (DIO-prone) or to be diet-resistant (DR-prone) when subsequently fed a high-energy diet. Under control conditions, both in vivo and in vitro studies showed DIO-prone rats to have reduced levels of low-, but not high-affinity [3H]glyburide binding in most forebrain areas. As compared to equiosmolar infusions of mannitol, 60 min unilateral intracarotid glucose infusions at 4 mg/kg/min in awake rats reduced low-affinity [3H]glyburide binding in numerous hypothalamic and amygdalar areas of both DR- and DIO-prone rats with little effect on high-affinity binding. Only in the paraventricular nucleus of DR-prone rats was there a phenotype-specific downregulation of low-affinity binding. Brain sections from other rats were incubated with [3H]glyburide in the presence of 0, 5 or 10 mM glucose. The resultant in vitro effects of glucose were more variable and widespread than intracarotid infusions. Here, glucose often increased low-affinity [3H]glyburide binding, particularly in DR-prone rats at 5 mM. Again, there was little effect on high-affinity binding. Thus, glucose may affect the firing of glucose-responsive neurons by indirectly altering KATP channel function via its effects on low-affinity cell body SUR.
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PMID:In vivo and in vitro regulation of [3H]glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucose. 943 7


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