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

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 aim of this study was to investigate the metabolic effects of short-term fasting in obese diabetic patients and to correlate the observed changes with the activity of hepatic key enzymes in an animal model of obesity-associated diabetes (ob/ob mice, C57BL/6J strain). In obese diabetic patients (ODP), a 72-h fast (causing slight change in body weight) decreased fasting glycemia by 3.82 +/- 0.79 mmoles/l and significantly improved glucose tolerance (OGTT) while reducing basal and stimulated insulinemia, whereas in obese non-diabetic patients (ONDP) only a small decrease in fasting glycemia (1.24 +/- 0.51 mmoles/l) occurred. This suggests that in ODP hyperphagia is a factor contributing to maintain hyperglycaemia and glucose intolerance (in the face of hyperinsulinaemia, indicating insulin resistance). In fed obese hyperglycaemic mice (OHM), which are a good model of the human obesity-associated diabetes, hepatic fructose-1,6-diphosphatase (F16Pase) and glucose-6-phosphatase (G6Pase), involved in glucose production, showed increased activity (+52 and +200 per cent, respectively) compared to control mice (CM), and the ratios of F16Pase and G6Pase to the opposing enzymes phosphofructokinase (PFK1) and glucokinase (GK), i.e. the F16Pase/PFK1 and G6Pase/GK ratios, were increased by 38 and 101 per cent, respectively, suggesting increase in gluconeogenesis and perhaps in glycogenolysis. In the 48-h fasted OHM, F16Pase activity was decreased (-30 per cent) compared to the fed animals, while the activity of G6Pase showed a smaller and statistically not significant change (-22 per cent). In contrast, in the CM a 48-h fasting was associated with a trend toward increased F16Pase (+22 per cent) and G6Pase (+173 per cent). However, since PFK1 and GK decreased to a similar extent in OHM and CM, the F16Pase/PFK1 and G6Pase/GK ratios, basally elevated in the OHM, did not change with fasting, whereas in the CM they showed a striking elevation (+71 and +274 per cent, respectively). The basally elevated F16Pase/PFK1 and G6Pase/GK ratios (functionally linked to glucose production) in the OHM may contribute to maintain hyperglycaemia; in these mice, the lack of further increase in the glucose production-related F16Pase/PFK1 and G6Pase/GK ratios (which occurs in CM) with fasting might allow that the interruption of the afflux of dietary carbohydrates ameliorates the glycaemic level. Similar mechanisms might occur also in the ODP.
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PMID:Metabolic effects of short-term fasting in obese hyperglycaemic humans and mice. 283 Nov 63

Seven cytoplasmic enzyme activities were measured in extracts of mononuclear leukocytes (lymphocytes plus monocytes) obtained from 19 type II diabetic humans and 10 healthy control subjects. 6-Phosphofructokinase activity was significantly decreased in cell extracts from diabetics, while other enzyme activities were similar in diabetics and controls. Since the effects of starvation on enzyme activities are sometimes similar to the effects of diabetes, the studies were repeated in 5 control subjects after a 2-day fast. This short period of starvation did not mimic the effect of diabetes on 6-phosphofructokinase activity. The decreased enzyme activity was not correlated with percent specific insulin binding to monocytes in the same cell preparations nor to clinical variables such as obesity or the broad range of fasting plasma glucose values encountered among the diabetics. We conclude that 6-phosphofructokinase activity in mononuclear leukocytes, as in other tissues, may be a marker for a postreceptor lesion associated with the insulin resistance found in type II diabetes mellitus.
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PMID:Impaired 6-phosphofructokinase activity in mononuclear leukocytes from patients with type II diabetes mellitus. 295 96

The influence of obesity on myocardial function and metabolism was studied in obese (fa/fa) and thin (Fa/Fa) Zucker rats using the isolated perfused heart as model. Cardiac performance of obese Zucker rats was not impaired. Instead, left ventricular pressure and contractility were increased as compared to controls. In agreement with these findings, creatine phosphate and the ratios of ATP/ADP and creatine phosphate creatine were elevated. The uptake and the conversion of glucose by hearts of obese Zucker rats were impaired. Insulin stimulated the uptake and oxidation of glucose. However, the responsiveness of these processes to insulin was diminished. Lipolysis of endogenous lipids was accelerated severalfold in obesity. Inhibition of fatty acid oxidation by a specific carnitine palmitoyl-transferase inhibitor, phenylalkyloxirane carboxylic acid (POCA), led to a slow rate of lipolysis, and to an acceleration of glucose oxidation and of the basal, noninsulin-dependent uptake of glucose. In the presence of POCA, insulin had, however, no additional stimulatory effect on the glucose uptake by hearts of obese rats. In contrast to hearts of ketotic, acutely diabetic rats where POCA fully restored myocardial responsiveness of glucose uptake and conversion to insulin, in hearts of obese rats only a shift in the glucose pathway from glycolytic formation of lactate and pyruvate to oxidation to CO2 was observed. Thus, POCA can be used as a tool to distinguish different forms of insulin resistance in obesity: 1) a lipid metabolism-dependent defect--presumably an inhibition of phosphofructokinase and pyruvate dehydrogenase by metabolites of fatty acid oxidation, influenced by inhibition of carnitine palmitoyltransferasei, and 2) a lipid metabolism-independent defect in the activation of uptake of glucose and glycogen synthesis by insulin not affected by POCA.
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PMID:Different types of postinsulin receptor defects contribute to insulin resistance in hearts of obese Zucker rats. 373 68

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

The activity ratio of phosphofructokinase in perfused rat heart and its activation by epinephrine was examined in non-obese, fat-fed obese, and genetically obese rats. For non-obese colony rats there was an age-dependent increase in the activity ratio of phosphofructokinase from 0.2 at 40 days to 0.4 at mature age (greater than 200 days). Epinephrine (10 microM) treatment of the heart for 5 min increased the ratio at all ages but the proportional increase diminished with age. For mature-age lean Zucker rats carrying the genetic determinant for obesity the results were similar to those obtained for comparable non-obese colony rats. For fat-fed obese rats the activity ratio of phosphofructokinase at 200 days of age was 0.2 and was increased to 0.6 by epinephrine treatment. For mature-age obese Zucker rats the activity ratio was 0.2 and no significant response to epinephrine occurred. The activity ratio of glycogen phosphorylase and its response to epinephrine (beta-adrenergic receptor mediated) in heart was unaffected by age, diet or the gene for obesity. The present findings indicate a specific defect in the adrenergic regulatory mechanism for phosphofructokinase in genetically obese rats.
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PMID:Obesity and the regulation of phosphofructokinase in heart: an apparent insensitivity to adrenergic activation in mature-age genetically obese rats. 629 Aug 38

To evaluate the relationships between changes in muscle morphology and metabolic adaptation to physical training in obesity, twenty obese women were subjected to a physical training programme with three sessions a week for 3 months. Physical training resulted in lowering of plasma insulin and improved glucose tolerance. Neither body weight nor body fat changed. With physical training the percentage distribution of fast twitch oxidative (FTa) muscle fibres (m vastus lateralis) increased (from 30.3 +/- 5.1% to 35.2 +/- 4.8%, P less than 0.05) and that of fast twitch glycolytic fibres decreased (from 18.3 +/- 6.6 to 5.8 +/- 4.8%, P less than 0.05). The number of capillaries increased, mainly around slow twitch (ST) fibres (from 4.5 +/- 0.6 to 5.8 +/- 0.8, P less than 0.01) and fast twitch oxidative (FTa) fibres (from 3.9 +/- 0.7 to 4.7 +/- 0.8, P less than 0.01). The activities of oxidative enzymes (cytochrome-c-oxidase and citrate synthase) increased (P less than 0.05) while those of glycolytic enzymes (phosphofructokinase and hexokinase) decreased after physical training (P less than 0.01). Significant negative correlations between plasma insulin and number of capillaries in contact with ST fibres (r = 0.80, P less than 0.001) and FTa fibres (r = 0.62, P less than 0.001) were found before training. The capillary density around those fibres could predict 80% of the explained variance of plasma insulin levels (P less than 0.001). The changes of glucose concentration after training could be predicted by observed changes in enzyme activities. The strong associations between muscle morphology and capillarization and enzyme activities and glucose and insulin concentrations and their changes after training suggest an important regulatory role of muscle which warrants further studies.
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PMID:Relationship between muscle morphology and metabolism in obese women: the effects of long-term physical training. 640 24

The regulatory kinetic properties of phosphofructokinase partially purified from the livers of C57BL/KsJ mice were studied. The fructose 6-phosphate saturation curves were highly pH dependent. At a fixed MgATP concentration (1 mM), allosteric kinetics was observed in the range of pH studied (7.3 to 8.3) and the S0.5 values for fructose 6-phosphate decreased by about 0.2 to 0.3 mM for each 0.1-unit increment in pH. Allosteric effects on the sigmoidal response to fructose 6-phosphate: activation by AMP, NH4+, and glucose 1,6-bisphosphate, inhibition by MgATP2-, and synergistic inhibition between ATP and citrate, were all present at pH 8.0 to 8.2. Comparative kinetic studies with liver phosphofructokinase isolated from both the normal (C57BL/KsJ) and the genetically diabetic (C57BL/KsJ-db) mice of 9 to 10 and 15 to 16 weeks of age showed that the enzyme from the livers of diabetic mice exhibited decreased activity at subsaturating concentrations of fructose 6-phosphate. However, phosphofructokinase isolated from the livers of normal and genetically diabetic mice of 4 to 5 weeks of age showed no difference in kinetic properties. Thus, there appears to be a correlation between the change in properties of liver phosphofructokinase and the expression of hyperglycemia and obesity in the genetically diabetic mice. The decreased activity of liver phosphofructokinase in the older diabetic animals may well be one of the causes of the increased blood glucose levels. The results are also discussed in a general context with regard to the possible role of phosphofructokinase in the regulation of hepatic gluconeogenesis.
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PMID:Mouse (C57BL/KsJ) liver phosphofructokinase. Allosteric kinetics and age-related changes in the genetically diabetic state. 645 Feb 2

The purpose of the current study was to examine the enzymatic profile [phosphofructokinase (PFK), beta-hydroxyacyl-CoA dehydrogenase (HADH), and citrate synthase (CS)] in gastrocnemius muscle, heart, and liver in rats allowed ad libitum access to a high-fat diet (HFD, 45% of kcal from corn oil). Male Wistar rats were fed a low-fat diet (LFD, 12% of kcal from corn oil) for a 2-wk baseline period after which some continued on the LFD and others were placed on the HFD. After 1 wk on the HFD, rats were categorized as obesity-resistant (OR), -intermediate (OI), or -prone (OP) on the basis of body weight gain (OR, lower tertile; OI, middle tertile; OP, upper tertile). At 1, 2, and 5 wk, rats from each group were killed (n = 9-14 from each group/time point) after a 24-h fast. At the end of the 5-wk dietary period, weight gain was 114.8 +/- 4.3 in LFD, 125.2 +/- 3.7 in OR, 147.1 +/- 4.1 in OI, and 173.7 +/- 3.5 g in OP rats (OP > OI > OR, LFD; P < 0.001). Energy intake was highly correlated with weight gain on the HFD at each time point (r > or = 0.72, P < 0.001). After 1 wk on the HFD, significant correlations between the ratio of PFK/HADH (an indication of the relative capacity for glycolysis vs. beta-oxidation, r = 0.4, P = 0.03) and HADH/CS (an indication of the capacity for beta-oxidation relative to total oxidative capacity, r = -0.56, P = 0.001) in the gastrocnemius muscle and weight gain were observed. At week 2, significant correlations between these ratios and weight gain were observed in the gastrocnemius, liver, and heart. In contrast, these ratios were not significantly correlated with weight gain at 5 wk. These results suggest that rats most susceptible to weight gain or a HFD are characterized by a continuous increase in energy intake (explaining approximately 50% of the variance in weight gain) and an early tissue enzymatic profile that favors carbohydrate over fat use.
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PMID:Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat-fed rats. 903 8

A number of biochemical defects have been identified in glucose metabolism within skeletal muscle in obesity, and positive effects of weight loss on insulin resistance are also well established. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity-related insulin resistance and of the effects of weight loss, though it is evident that muscle contains increased triglyceride. The current study was therefore undertaken to profile markers of human skeletal muscle for fatty acid metabolism in relation to obesity, in relation to the phenotype of insulin-resistant glucose metabolism, and to examine the effects of weight loss. Fifty-five men and women, lean and obese, with normal glucose tolerance underwent percutaneous biopsy of vastus lateralis skeletal muscle for determination of HADH, CPT, heparin-releasable (Hr) and tissue-extractable (Ext) LPL, CS, COX, PFK, and GAPDH enzyme activities, and content of cytosolic and plasma membrane FABP. Insulin sensitivity was measured using the euglycemic clamp method. DEXA was used to measure FM and FFM. In skeletal muscle of obese individuals, CPT, CS, and COX activities were lower while, conversely, they had a higher or similar content of FABP(C) and FABP(PM) than in lean individuals. Hr and Ext LPL activities were similar in both groups. In multivariate and simple regression analyses, there were significant correlations between insulin resistance and several markers of FA metabolism, notably, CPT and FABP(PM). These data suggest that in obesity-related insulin resistance, the metabolic capacity of skeletal muscle appears to be organized toward fat esterification rather than oxidation and that dietary-induced weight loss does not correct this disposition.
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PMID:Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. 1054 88


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