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

Rats were overfed during the suckling period by litter size manipulation in order to investigate the possible contribution of preadipocytes from the stroma-vascular compartment of adipose tissue to the development of obesity. Rats raised in litters of four pups were overfed; for normal feeding we assigned eight pups per litter. As early as 10 d of age, overfed rats became fatter than controls, and showed an increase in both plasma insulin and triacylglycerol levels. At this age, adipose tissue overdevelopment arose only from adipocyte hypertrophy, since hyperplasia occurred only at 15 d of age. Concurrently, compared to normal feeding, overfeeding led to significantly higher activities of lipoprotein lipase (LPL), glycerophosphate dehydrogenase (GPDH) and glycerophosphate acyltransferase (GPAT) in mature fat cells; 10-d-old overfed pups exhibited a higher stromal cell number. Further separation of this heterogeneous fraction by density gradient centrifugation showed a higher preadipocyte number as compared to that of controls. In stromal cells, LPL, GPDH, GPAT and acyl CoA ligase activities were detected during the suckling period. As compared to controls, overfeeding induced an increase in both LPL and GPDH activities in 10-d-old pups. Results indicate that overfeeding in early life induced an excess of fat storage capacity through a simultaneous increase in proliferation and differentiation rates of adipocyte precursors.
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PMID:Role of adipocyte precursors in the onset of obesity induced by overfeeding in suckling rats. 395

Synthesis of fatty acids was measured in the liver and in epididymal adipose tissue of sand rats and albino rats. In chow-fed sand rats the rate of hepatic lipogenesis, as measured by the incorporation of 3H2O into fatty acids, was four- to sevenfold higher than in albino rats and in sand rats on a low-calorie saltbush diet. The contribution of [14C]glucose to lipogenesis in sand rat liver was lower than in albino rats. In fed sand rats lipogenesis incorporating 3H2O was stimulated by casein but not by glucose. In adipose tissue, lipogenesis measured 1 h after administration of 3H2O was much lower in sand rats than in albino rats. In vitro incorporation of [14C]glucose or acetate into adipose tissue fatty acids was negligible. In adipose tissue, uptake of very-low-density lipoproteins (VLDL) and lipoprotein lipase activity were sevenfold higher than in albino rats. Activities of NADP-malate dehydrogenase, acetyl CoA carboxylase, and fatty acid synthetase were considerably higher in the liver of chow-fed sand rats than in albino rats. It was concluded that obesity in sand rats originates from hepatic lipogenesis without a significant contribution of local fatty acid synthesis in adipose tissue.
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PMID:Lipogenesis in the sand rat (Psammomys obesus). 634 15

Zucker rats were early weaned onto either medium-chain (MCT) or long-chain triglycerides (LCT) to examine the effect on the development of obesity. Preobese and lean pups were weaned at 16 days to isocaloric, isonitrogenous liquid diets containing either 65% MCT or LCT (by calories) or to a "stocklike" (5.5% fat, 72.6% carbohydrate) control diet or were pair-fed stocklike diet to MCT-fed rats until day 45. MCT-feeding lowered body weight gain and fat pad weight in obese and lean rats compared to stocklike-fed controls. Additionally, fat cell size and lipoprotein lipase (LPL) activity and hepatic acetyl CoA carboxylase activity were reduced in obese MCT-fed rats compared to obese controls fed stocklike diet. Except for altered LPL activity the effects produced by MCT-feeding were attributable to its anorectic effect. However, all obese rats, including the MCT group, developed an obese body composition and were hyperinsulinemic. The development sequence leading to obesity may be derived from a fundamental cellular defect that results in metabolic alterations in different tissues at critical periods of development. Thus, effective treatment of this genetic obesity requires a better understanding of fa gene action.
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PMID:Effect of high fat weanling diets containing either medium-chain triglycerides or long-chain triglycerides on the development of obesity in the Zucker rat. 704 90

Obesity is often associated with an elevated total body cholesterol synthesis. In order to evaluate the role of hepatic cholesterogenesis in this phenomenon, we assayed the rate-limiting step in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in the microsomal fraction of liver biopsies obtained operatively from ten morbidly obese (relative body weight greater than 155%) subjects. Eighteen normal-weight patients (relative body weight less than 120%) with cholesterol gallstones served as controls. Hepatic HMG CoA reductase activity, expressed as pmol X min-1 X mg protein-1, was 60% higher in the obese subjects compared to the gallstone patients (P less than 0.05). Microsomal protein concentration was lower in the obese patients, so that enzyme activity calculated per gram liver was not significantly different between the two groups. However, mevalonate formation, expressed in terms of total organ activity, was higher in the obese than in the nonobese group. The results suggest that the liver is a major contributor to the increased cholesterol production seen in obesity.
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PMID:Hepatic cholesterol metabolism in obesity: activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase. 711 74

This chapter focuses on the biochemical mechanisms that mediate glucose-stimulated insulin secretion (GSIS) from beta-cells of the islets of Langerhans and the potentiating role played by fatty acids. We summarize evidence supporting the idea that glucose metabolism is required for GSIS and that the GLUT-2 facilitated glucose transporter and the glucose phosphorylating enzyme glucokinase play important roles in measuring changes in extracellular glucose concentration. The idea that glucose metabolism is linked to insulin secretion through a sequence of events involving changes in ATP:ADP ratio, inhibition of ATP-sensitive K+ channels, and activation of voltage-gated Ca2+ channels is critically reviewed, and the relative importance of ATP generated from glycolytic versus mitochondrial metabolism is evaluated. We also present the growing concept that an important signal for insulin secretion may reside at the linkage between glucose and lipid metabolism, specifically the generation of the regulatory molecule malonyl CoA that promotes fatty acid esterification and inhibits oxidation. Finally, we show that in contrast to its short term potentiating effect on GSIS, long-term exposure of islets to high levels of fatty acids results in beta-cell dysfunction, suggesting that hyperlipidemia associated with obesity may play a causal role in the diminished GSIS characteristic of non insulin-dependent diabetes mellitus (NIDDM).
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PMID:Metabolic coupling factors in pancreatic beta-cell signal transduction. 757 98

We review evidence that increased tissue levels of fatty acyl CoA cause the beta-cell abnormalities of nondiabetic obesity and ultimately result in obesity-dependent diabetes. Nondiabetic obesity in Zucker rats is characterized by hypersecretion of insulin at normal fasting and subfasting glucose concentrations. This is a result of beta-cell hyperplasia and increased low Km glucose usage and oxidation. These abnormalities, the hyperinsulinemia, the hyperplasia of beta-cells, i.e., its in vitro equivalent, enhanced bromodeoxyuridine incorporation, and the increased low Km glucose usage can be induced by culturing normal islets with 2 mmol/l free fatty acids (FFAs). Once obese Zucker diabetic fatty rats become diabetic, glucose-stimulated insulin secretion (GSIS) is absent and beta-cell GLUT2 reduced. Islet triglyceride (TG) content is increased 10-fold, probably reflecting increased FFA delivery (plasma FFA levels > 1.5 mmol/l) beginning about 2 weeks before the onset of diabetes. These beta-cell abnormalities, GSIS loss, GLUT2 loss, and TG accumulation, are prevented by reducing plasma FFAs by caloric restriction and by nicotinamide injection. The loss of GSIS and the accumulation of TGs, but not the GLUT2 loss, can be induced in vitro in normal islets cultured in a 2 mmol/l FFA-containing medium, but prediabetic islets seem far more vulnerable to FFA-induced functional impairment and TG accumulation. It is proposed that in uncomplicated obesity, increased lipid availability (FFA levels < 1.5 mmol/l) induces both hyperinsulinemia and insulin resistance in parallel fashion, thereby maintaining normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. 762 89

Obesity is often associated with an increased hepatic secretion rate of cholesterol and saturated gallbladder bile. In order to evaluate the role of hepatic esterification of cholesterol in this phenomenon, we assayed the activity of acyl CoA:cholesterol acyl transferase (ACAT), which catalyzes the esterification of cholesterol, in liver microsomes obtained from 19 morbidly obese patients without gallstones undergoing vertical banded gastroplasty. Gallbladder bile was obtained and analyzed for lipid composition, cholesterol saturation, nucleation time, and occurrence of cholesterol crystals. Fourteen non-obese gallstone-free subjects undergoing cholecystectomy because of suspected polyp or adenomyoma in the gallbladder served as controls. The hepatic content of esterified cholesterol was increased by about 70% in the obese patients (P < 0.05). Still, the mean levels of the ACAT activity were equal in the obese and non-obese patient groups (11 +/- 1 and 11 +/- 2 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system, the activity was increased markedly in both groups. The ACAT activity was higher in obese patients with steatosis of the liver compared with those displaying normal liver morphology (12 +/- 1 vs 8 +/- 1 pmol/min per mg, P < 0.05). Obese patients did not have significantly more saturated gallbladder bile than the non-obese controls (84 +/- 7 and 77 +/- 8%, respectively). They had a normal nucleation time and their gallbladder bile did not contain any cholesterol crystals. We conclude that obese patients without gallstones usually have a normal esterification rate of cholesterol in the liver. Steatosis of the liver was associated with increased ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic esterification rate of cholesterol and biliary lipids in human obesity. 801 83

Werner syndrome (WS) is a rare autosomal recessive disease with poor growth, premature aging, scleroderma-like skin changes, endocrine abnormalities, and deficiencies of adipose tissue. Could there be a genetic obesity syndrome which offers an instructive contrast to at least one form of WS? At least one form of WS might result from an enzyme defect that causes hypertriglyceridemia, hyperinsulinism, and hyperglucagonism; the defective enzyme might play a key role in the utilization of tryptophan, riboflavin (vitamin B2), or other vitamins or in the synthesis of prostaglandins that inhibit insulin secretion. At least one form of genetic obesity might result from an enzyme defect that causes hypotriglyceridemia and hyperinsulinism without hyperglucagonism; the defective enzyme might be unable to bind properly to a product that inhibits some step in the process of conversion of free fatty acid (FFA) CoA into ketoacids.
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PMID:Werner syndrome and genetic obesity: speculation. 852 89

These studies were designed to assess the effects of pioglitazone, a new oral antidiabetic agent that acts by improving insulin sensitivity, on blood pressure, plasma and tissue lipids, and insulin resistance in the Dahl salt-sensitive (Dahl-S) rat. Reaven et al had reported that male Dahl-S rats are moderately hyperinsulinemic and insulin-resistant. This was of particular interest since these rats are not obese but are hypertriglyceridemic, and on a high-salt diet they become hypertensive. In the current study, male Sprague-Dawley control and Dahl-S rats were compared when fed standard chow of high-fat, high-sucrose (HFHS) diets with or without pioglitazone (20 mg/kg body weight/d) for 3 weeks. On the standard chow diet, Dahl-S rats were hypertriglyceridemic and had high tissue levels of malonyl coenzyme A ([CoA] Dahl-S 5.0 v control 3.3 nmol/g in muscle, and Dahl-S 15.6 v control 10.7 nmol/g in liver); however, they were not hyperinsulinemic. Pioglitazone therapy decreased both malonyl CoA and plasma triglycerides toward control values, but had no effect on plasma insulin levels. On the HFHS diet, both groups became glucose-intolerant and hyperinsulinemic; however, the hyperinsulinemia was greater and more sustained in Dahl-S rats. In addition, the HFHS diet appeared to increase the mass of retroperitoneal fat in the Dahl-S but not in the control group. Treatment with pioglitazone decreased retroperitoneal fat, but as reported previously, it increased the mass of the epididymal fat pad. The results suggest that the hypertriglyceridemia of the Dahl-S rat is associated with an increase in the concentration of malonyl CoA in both liver and muscle. They also show that pioglitazone reverses both of these abnormalities independently of its effect on plasma insulin. Whether these high levels of malonyl CoA predispose the Dahl-S rat to hyperinsulinemia and possibly obesity when placed on a HFHS diet remains to be determined.
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PMID:Malonyl coenzyme A and adiposity in the Dahl salt-sensitive rat: effects of pioglitazone. 860 42

Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very-low-calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis. Obese subjects were randomized to one of two low-calorie liquid diets for rapid weight loss: a 520-kcal diet with less than 2 g fat/d, and a 900-kcal diet with 30 g fat/d (including one 10-g fat meal to stimulate maximal gallbladder emptying). Bile and blood lipids, saturation index, leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity, and ultrasonographic gallbladder emptying were measured repeatedly during dietary treatment. Both diets produced comparable weight loss of 22%. Bile cholesterol saturation index increased during both diets (26%), but fell to 15% below prediet level after weight loss. Compared with subjects' maximal gallbladder emptying fraction of 66%, the 520-kcal diet provided poor gallbladder emptying (35%), whereas the 10-g fat meal of the 900-kcal diet provided maximal emptying. Gallstones developed in four of six 520-kcal subjects and none of seven 900-kcal subjects (P = .021), an unanticipated difference that resulted in premature study termination for ethical reasons. Blood lipids and HMG CoA reductase activity in mononuclear leukocytes fell at week 8 during both diets, but recovered while weight was still being lost. The findings suggest that gallstone risk during rapid weight loss may be reduced by maintenance of gallbladder emptying with a small amount of dietary fat. Ultimately, weight loss reduced bile cholesterol saturation and improved highdensity lipoprotein (HDL) levels.
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PMID:The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss. 878 21


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