Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lean mice were made obese by feeding, ad libitum, a high-lard diet. They showed an increased fat cell size and number which were maintained when this diet was replaced by the control high-carbohydrate diet for 10 weeks. Obese fed mice showed normal glucose and insulin serum levels, but insulinaemia was elevated after an overnight fast. The insulinaemic response after intraperitoneal injection of glucose was insignificant. Thus hyperinsulinism is not a prerequisite for the development of obesity. High-fat diet influenced, in vitro, glucose metabolism of adipose tissue, liver and muscle: basal lipogenesis was markedly reduced in adipose tissue and liver, and glucose oxidation was decreased in muscle. Insulin sensitivity was reduced by increased fat cell size. De novo formation of fatty acids in liver and adipose tissue did not contribute to the development of obesity. The increased lipoprotein lipase activity of the large fat cells suggested that obesity resulted from a direct storage of dietary fatty acids esterified by glycerol formed from circulating glucose.
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PMID:Metabolism of the mouse made obese by a high-fat diet. 123 69

In this study of spontaneous obesity of pigs, specific metabolic shifts were observed, which explain an increase in fat deposition. Liver tissue utilization of pyruvate and glucose for oxidation and lipogenesis showed no significant difference between lean and obese pigs. Adipose tissue utilization of glucose, acetate and glycerol for triglyceride and fatty acid synthesis was greater in obese pigs than lean pigs (P less than 0.01). No significant difference in leucine incorporation into lipid fractions was found. Of the substrates utilized, glucose supplied 86 and 94% of the glyceride-glycerol synthesized in lean and obese pigs, respectively. Glycerol was not a major contributor to glyceride-glycerol synthesis (3.5 to 5.5%), in spite of the presence of adipose tissue glycerokinase. An increase (P less than 0.05) in alanine incorporation into glucose was observed in liver tissue from obese pigs. In general, the levels of enzymes activities associated with gluconeogenesis, glycolysis, and lipogenesis supported the findings of in vitro utilization of these substrates.
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PMID:A comparison of the enzyme levels and the in vitro utilization of various substrates for lipogenesis in pair-fed lean and obese pigs. 125 Aug 52

The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.
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PMID:Basal intermediary metabolism in impaired glucose tolerance and morbid obesity. 134 2

BRL 26830A is a thermogenic beta-adrenergic agonist drug which has an anti-obesity effect in animals and diet-restricted obese man. This study was undertaken in obese subjects who were not calorie restricted to assess the effect of three weeks drug administration on energy expenditure and glucose, amino acid and fatty acid metabolism in the post-absorptive and fed states. Stable isotope tracers were employed to determine kinetic data both at baseline and during adrenaline infusion. There was no evidence of BRL 26830A causing a major shift in fuel metabolism or having an anabolic effect. Baseline plasma concentrations of glycerol (P less than 0.01) and palmitate (P less than 0.01) were reduced, glucose remained within the normal range, whereas insulin decreased after BRL 26830A. The hypoaminoacidaemic effect of adrenaline was attenuated by BRL 26830A (P less than 0.01 for branched-chain amino acids, P less than 0.05 for total amino acids). The results suggest that BRL 26830A improves insulin sensitivity and causes selective down-regulation of adrenergic receptors. The increased insulin sensitivity may be a useful therapeutic effect for this class of drug and suggests a possible role in the treatment of obese non-insulin dependent diabetic patients.
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PMID:Metabolic effects of three weeks administration of the beta-adrenoceptor agonist BRL 26830A. 135 39

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study. 147 41

To estimate the regional subcutaneous glycerol production rate in normal and obese humans, the venous arterialized plasma glycerol, interstitial glycerol in the subcutaneous adipose tissue together with adipose tissue blood flow (ATBF, ml/100 g.min) were measured in the postabsorptive state and for 2 h after ingestion of 100 g of oral glucose. Eight lean and eight obese men with normal oral glucose tolerance tests were investigated with the subcutaneous microdialysis technique and 133Xe clearance. In the postabsorptive state, the interstitial glycerol concentrations in lean and obese subjects were 170 +/- 21 vs. 282 +/- 28 microM (P less than 0.01) and 156 +/- 23 vs. 225 +/- 12 microM (P less than 0.05) in the abdominal and femoral subcutaneous adipose tissue, respectively. The corresponding arterial glycerol levels were 54 +/- 4 vs. 75 +/- 14 microM (NS). Abdominal ATBF was greater in lean subjects (3.2 +/- 0.6 vs. 1.6 +/- 0.3; P less than 0.05), whereas femoral ATBF was similar in both groups (2.7 +/- 0.4 vs. 2.4 +/- 0.7). Estimated mean local glycerol release (mumol/100 g.min) was similar in the lean and obese group (0.16 +/- 0.03 vs. 0.20 +/- 0.05 and 0.18 +/- 0.02 vs. 0.17 +/- 0.04) in the abdominal and femoral site, respectively. We conclude that glycerol production from the subcutaneous tissue is increased in obesity, irrespective of adipose tissue distribution. This enhancement is due to the increased adipose tissue mass.
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PMID:Glycerol production in subcutaneous adipose tissue in lean and obese humans. 156 99

To study the initial period of fat deposition in human obesity, we measured glycerol turnover in 12 children of 135-253% ideal body weight, who had continuously gained weight since the onset of obesity 2-9 yr previously. Hyperinsulinemia developed in these children depending on obesity duration (r = 0.74, P less than 0.01). Whole-body glycerol production was twofold greater in the obese children (311 vs. 156 mumol.min-1, P less than 0.01) and correlated with body fat (r = 0.67, P less than 0.005). Normalization of glycerol flux to fat mass revealed that the rate of triglyceride hydrolysis was in fact lower in the adipose tissue of obese children (9.4 vs. 17.7 mumol.min-1/kg body fat) and correlated with plasma insulin (r = 0.64, P less than 0.005). Euglycemic insulin clamps showed that the response of glycerol production to a unit increment in plasma insulin concentration was increased in obese children, suggesting increased insulin sensitivity of adipose tissue. As a direct consequence (r = 0.67, P less than 0.025) of their elevated plasma glycerol concentration (65 +/- 4 vs. 37 +/- 2 microM, P less than 0.05) obese children had an increased glycerol utilization by the whole body, as well as per unit of lean body mass (9.1 +/- 1 vs. 6.5 +/- 0.9 mumoles.min-1.kg lean body mass-1, P less than 0.025).
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PMID:Glycerol production and utilization during the early phase of human obesity. 160 71

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion. 164 Aug 47

This study was initiated to elucidate the mechanisms behind valproate-induced weight gain. Eight patients with epilepsy were studied with identical examination programs before and during the end of the first month of treatment with sodium valproate (VPA). The measurements included registration of food intake, indirect calorimetry, and determination of pancreatic and thyroid hormones, catecholamines, albumin, electrolytes, glycerol, and free fatty acids. Measurements were performed both at the basal condition and during a 3-hour oral glucose tolerance test (OGTT). After the start of VPA treatment, the mean levels during the OGTT of plasma glucose and catecholamines were significantly decreased by 7% and 25%, respectively (P less than .05). The mean ratio of insulin to glucagon decreased by 37% (P less than .01). During the glucose load, the decreases in free fatty acids were less pronounced after the start of VPA treatment, whereas the mean levels of glycerol were found to be unchanged. We detected no differences between the two periods with regard to total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. As VPA is known to affect the concentration of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance.
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PMID:Metabolic changes during treatment with valproate in humans: implication for untoward weight gain. 164 Aug 53

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.
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PMID:Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance. 175 24


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