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

Estimates of the activities (Vmax) of six enzymes involved in de novo fat synthesis were made in replicated lines of mice differing in fat content. These lines had been selected high and low for 20 generations with three replicates each of Fat, Control and Lean lines and for a further eight generations high and low as an unreplicated line. The activities of ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS), cytoplasmic malate dehydrogenase (MDH), malic enzyme (ME) and pyruvate kinase (PK) were determined in vitro in both liver and gonadal fatpad tissues taken at ages five and ten weeks. The activities of ACL, ACC, FAS and ME were significantly higher in the Fat than the Lean lines, and the differences were more pronounced at the earlier age and in the gonadal fatpad where activities in the Fat lines were higher by factors of 3.5, 2.4, 2.5 and 3.5 respectively. The activity of PK was unchanged in each tissue. MDH activity was significantly lower in adipose tissue in the Fat lines than the Lean lines at age ten weeks but not at age five weeks or in liver tissue. Results from replicates indicated that random genetic drift affected enzyme activities but nevertheless significant changes in activity were associated with the direction of selection. The changes in enzyme activity reported here are similar to those known to be associated with major mutations causing obesity in mice.
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PMID:Analysis of lines of mice selected for fat content. 2. Correlated responses in the activities of enzymes involved in lipogenesis. 196 75

Twenty obese and 20 lean LA/N-cp male rats and 20 male Sprague-Dawley rats were fed a diet containing either 54 percent sucrose or starch for six weeks. After a 14-16 hour fast, rats were killed. Liver and kidney enzyme activities were determined in the LA/N-cp rats while plasma urea and selected amino acids were determined in all rats. Liver glucose-6-phosphatase (G6PASE), fructose-1,6-bisphosphatase (FBPASE), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), glucokinase (GK), pyruvate kinase (PK), phosphofructokinase (PFK), glutamic-oxaloacetic-transaminase (GOT), glutamic-pyruvic transaminase (GPT), arginase (ARGASE), arginine-synthase (ARG-SYN) and ornithine transcarbamylase (OTC) levels were significantly affected by phenotype (obese greater than lean). All the above changes in enzyme levels were exaggerated by sucrose-feeding with the exception of PK, PFK, GOT, GPT, ARGASE and ARG-SYN. Kidney cortex G6PASE, PEPCK and ARGASE activities were higher in the obese rats as compared to the lean littermates. Sucrose feeding resulted in higher cortex G6PASE, FBPASE and PEPCK as compared to starch-fed rats. A phenotype effect was noted with plasma glutamate, urea, leucine, isoleucine and valine (obese greater than lean) and a diet effect was seen with aspartate, phenylalanine, leucine and valine (sucrose greater than starch) concentration. Sprague-Dawley rats had higher plasma urea and lower alanine than lean LA/N-cp males. Metabolic obesity in the LA/N-cp rat appears to involve an elevated capacity for pathways of glycolysis, gluconeogensis, lipogenesis and amino acid catabolism in the liver.
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PMID:Effect of dietary carbohydrate on liver and kidney enzyme activities and plasma amino acids in the LA/N-cp rat. 204 12

The possibility that the glucocorticoid-dependence of obesity of the obese fa/fa rat reflects on overactivity of glucocorticoids on the brain has been investigated by studies of enzyme activities and glucocorticoid type II (GR) receptors. The activity of 2 glucocorticoid-sensitive enzymes, glycerol-3-phosphate dehydrogenase and glutamine synthetase, were increased in the hippocampus of obese rats. In contrast malate dehydrogenase and pyruvate kinase, glucocorticoid-insensitive enzymes, were normal. Adrenalectomy of obese rats reduced glycerol-3-phosphate dehydrogenase activity to the level of lean rats. Scatchard analysis of [3H]corticosterone binding showed that the number of type II (GR) receptors was increased in the hypothalamus and hippocampus of obese rats but the affinity of these receptors was reduced. The evidence supports the hypothesis of excessive central glucocorticoid activity in the obese rat.
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PMID:Increased type II glucocorticoid-receptor numbers and glucocorticoid-sensitive enzyme activities in the brain of the obese Zucker rat. 228 43

Metabolic alterations in ventromedial hypothalamus (VMH)-lesioned rats were investigated by examining daily changes of enzyme activities and urea concentrations three weeks after the operation. VMH-lesions in female adult rats caused a significant elevation in the activity of acetyl-CoA carboxylase in the liver and parametrial adipose tissue. These changes suggest an increased lipogenesis. VMH-lesions also elicited an increase in activities of glucokinase (GK), pyruvate kinase (PK) and fructose 1,6-bisphosphatase (FBPase), and a decrease in activities of phosphofructokinase (PFK), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. The apparently inconsistent changes in activities of key glycolytic enzymes, GK, PK and PFK, and key gluconeogenic enzymes, G6Pase, PEPCK and FBPase in the liver may be explained by the fact that they were favorable for glucose oxidation through pentose phosphate cycle and provide NADPH for lipogenesis in the liver. Furthermore, VMH-lesions induced an increase in urea contents of the liver and serum, and elicited an increase in activity of liver tyrosine aminotransferase (TAT) and a decrease in activity of liver histidase. These changes suggest an accelerated amino acid and protein catabolism, and favor an increment in the supply of the substrate for lipogenesis. Daily rhythms of TAT, histidase activities and serum urea concentration observed in the control rats were abolished by VMH-lesions. These findings suggest that VMH-lesions elicit the loss of these daily rhythms, probably through the disturbance of the circadian rhythm of feeding behavior at this dynamic phase (three weeks after operation) of obesity.
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PMID:Shift of metabolism in rats with ventromedial hypothalamic lesions with respect to changes in daily rhythms of enzyme activity. 614 67

Altered erythrocyte sodium potassium (Na,K)-stimulated adenosine triphosphatase (ATPase) activity has been cited as having pathophysiologic significance in morbidly obese man. Previous studies have failed to consider obese patients after weight loss and, therefore, did not clarify the role of ATPase deficiency as a cause or effect of the obese state. To define more completely the possible alteration of cellular thermogenesis in obesity, a study was made of three groups of people: (1) normal weight controls; (2) morbidly obese; and (3) formerly morbidly obese patients who had lost over 100 pounds after gastric bypass surgery. Erythrocyte ATPase activity was determined by use of an assay that coupled ATPase activity with NADH oxidation in the presence of excess pyruvate kinase, lactic dehydrogenase, and phosphoenolpyruvate. This coupled assay produced a continuous slope so that activity could be calculated from the initial, maximal, linear portion of the decay trace. Results did not demonstrate any statistically significant differences in Na,K-ATPase activity between groups by analysis of variance. A nonsignificant correlation of 0.086 was seen between obesity index and Na,K-ATPase activity. It is concluded that (1) erythrocyte Na,K-ATPase activity is similar in both normal and obese individuals, (2) erythrocyte Na,K-ATPase does not change with weight loss, and (3) therefore, disordered erythrocyte thermogenesis does not have a role in the development or maintenance of obesity.
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PMID:Erythrocyte sodium-potassium-stimulated adenosine triphosphatase activity is not related to obesity. 630 95

Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.
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PMID:A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. 1147 Sep 16

A number of tissues such as the brain must be continuously provided with glucose to meet their energy demand. In contrast, carbohydrate absorption during meals is a discontinuous process. Thus, we must store glucose when its is provided, release it or spare it when it is less abundant. Insulin, secreted by the pancreatic beta-cell is a key hormone in the adaptations of metabolic pathways linked to glucose homeostasis. It inhibits hepatic glucose production, promotes glucose storage in the liver and glucose uptake and storage in muscles and adipose tissues. This is achieved through the modifications of the activity of existing proteins (enzymes, transporters) but also through the regulation of gene expression. In the liver, when the diet is rich in carbohydrates, insulin is secreted and stimulates the expression of genes involved in glucose utilization (glucokinase, L-pyruvate kinase, lipogenic enzymes) and inhibits genes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes were poorly understood. Recently, the transcription factor Sterol Regulatory Element Binding Protein-1c (SREBP-1c) has been proposed as a key mediator of insulin transcriptional effects. Insulin increases the synthesis and nuclear abundance of this factor which when overexpressed in the liver mimics the effects of insulin on insulin-sensitive genes. This suggests that SREBP-1c could be involved in pathologies such as type 2 diabetes, obesity and more generally in insulin resistance syndromes.
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PMID:[Regulation of carbohydrate metabolism by insulin: role of transcription factor SREBP-1c in the hepatic transcriptional effects of the hormone]. 1183 61

Feeding a high carbohydrate diet induces transcription of more than 15 genes involved in the metabolic conversion of glucose to fat. A new transcription factor binding to a glucose response element of the pyruvate kinase and lipogenesis enzyme genes was discovered recently. This factor, termed carbohydrate responsive element-binding protein (ChREBP), is activated in response to high glucose and up-regulates these genes. Cyclic AMP and a high fat diet inhibit ChREBP and slow down glucose utilization. ChREBP is able to control transcription of lipogenic enzyme genes in response to nutritional and hormonal inputs, and may play an important role in disease states such as diabetes, obesity, and hypertension.
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PMID:Carbohydrate responsive element-binding protein (ChREBP): a key regulator of glucose metabolism and fat storage. 1211 Mar 66

Hepatocyte nuclear factors-3 (Foxa-1-3) are winged forkhead transcription factors that regulate gene expression in the liver and pancreatic islets and are required for normal metabolism. Here we show that Foxa-2 is expressed in preadipocytes and induced de novo in adipocytes of genetic and diet-induced rodent models of obesity. In preadipocytes Foxa-2 inhibits adipocyte differentiation by activating transcription of the Pref-1 gene. Foxa-2 and Pref-1 expression can be enhanced in primary preadipocytes by growth hormone, suggesting that the antiadipogenic activity of growth hormone is mediated by Foxa-2. In differentiated adipocytes Foxa-2 expression leads to induction of gene expression involved in glucose and fat metabolism, including glucose transporter-4, hexokinase-2, muscle-pyruvate kinase, hormone-sensitive lipase, and uncoupling proteins-2 and -3. Diet-induced obese mice with haploinsufficiency in Foxa-2 (Foxa-2+/-) develop increased adiposity compared with wild-type littermates as a result of decreased energy expenditure. Furthermore, adipocytes of these Foxa-2+/- mice exhibit defects in glucose uptake and metabolism. These data suggest that Foxa-2 plays an important role as a physiological regulator of adipocyte differentiation and metabolism.
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PMID:Role of Foxa-2 in adipocyte metabolism and differentiation. 1286 19

Alterations in hepatic glucose metabolism play a key role in the development of the hyperglycemia observed in type 2 diabetes. Because the transcription factor c-Myc induces hepatic glucose uptake and utilization and blocks gluconeogenesis, we examined whether hepatic overexpression of c-myc counteracts the insulin resistance induced by a high-fat diet. After 3 months on this diet, control mice became obese, hyperglycemic, and hyperinsulinemic, indicating that they had developed insulin resistance. In contrast, transgenic mice remained lean and showed improved glucose disposal and normal levels of blood glucose and insulin, indicating that they had developed neither obesity nor insulin resistance. These findings were concomitant with normalization of hepatic glucokinase and pyruvate kinase gene expression and enzyme activity, which led to normalization of intrahepatic glucose-6-phosphate and glycogen content. In the liver of control mice fed a high-fat diet, the expression of genes encoding proteins that control energy metabolism, such as sterol receptor element binding protein 1-c, peroxisome proliferator activated receptor alpha, and uncoupling protein-2, was altered. In contrast, in the liver of transgenic mice fed a high-fat diet, the expression of these genes was normal. These results suggest that c-myc overexpression counteracted the obesity and insulin resistance induced by a high-fat diet by modulating the expression of genes that regulate hepatic metabolism.
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PMID:Overexpression of c-myc in the liver prevents obesity and insulin resistance. 1295 86


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