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

Recent studies have found that angiotensinogen is expressed in white and brown fat pads, and adipocytes have been implicated as a primary source of angiotensinogen in several other tissues. The functional significance of this unexpected expression is unknown. To address this, we studied angiotensinogen messenger RNA (mRNA) expression and angiotensinogen secretion in adipose tissue and isolated adipocytes comparing fasted and refed rodents and those with genetic obesity with normal controls. Control 2-month-old Sprague-Dawley rats, those fasted for 3 days, or those fasted for 2 days and refed for 6 days were killed, and adipocytes were isolated from epididymal fat pads using collagenase digestion. Angiotensinogen mRNA was reduced to 14.6 +/- 2.3% of control levels under fasted conditions and increased to 228 +/- 53% of control levels after refeeding. Angiotensinogen release from adipocytes was reduced to 33% of control levels by fasting and increased to 183% by refeeding. These effects of fasting and refeeding on angiotensinogen regulation were tissue specific since liver angiotensinogen mRNA and serum angiotensinogen concentrations were unaffected. Systolic blood pressure, however, was modulated by fasting and refeeding in a manner parallel to adipocyte angiotensinogen expression. In related experiments, angiotensinogen secretion per epididymal fat pad of the ob/ob mouse model of obesity was increased an average of 3.4-fold compared with control. We conclude angiotensinogen expression in white adipocytes is regulated nutritionally in a tissue-specific manner. We propose that adipocyte angiotensinogen could play a previously unrecognized role in regulating adipose tissue blood supply and thereby fatty acid efflux from fat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. 155 65

To determine the effect of obesity on the size distribution of fat cell populations in human adipose tissue, omental fat tissue biopsies were obtained from lean, moderately obese, and massively obese patients. The size distributions of adipocytes from lean and obese fat tissues examined by the scanning electron microscopic method were bimodal, consisting of populations of very small fat cells and mature fat cells, in contrast to collagenase-derived isolated cells that showed only the large mature fat cells. The very small fat cell population represented 21 to 26% of the total fat cell number in the lean and in both obese groups. In contrast, preparations of human fat cells isolated by the collagenase method systematically excluded the very small fat cells. In massive obesity, both cell populations participated in the hyperplastic growth but only the larger mature fat cells increased in size, implying that these two cell populations differ in their physiological role.
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PMID:Scanning electron microscopy of very small fat cells and mature fat cells in human obesity. 271 32

Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. We have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37 degrees C with 10 micrograms/ml 125I-HDL2 or 125I-HDL3. In both depots, the cellular uptake of 125I-HDL2 and 125I-HDL3 was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of 125I-HDL2 and 125I-HDL3. In obese patients, the uptake of 125I-HDL was higher in subcutaneous cells than in omental cells [5.85 +/- 0.53 vs. 2.74 +/- 0.30 pmol X 2 h-1. (10(6) cells)-1]. The cellular 125I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional variation in HDL metabolism in human fat cells: effect of cell size. 357 14

The insulin binding properties and the molecular weights of the insulin receptor and its insulin binding subunit were studied in omental and subcutaneous adipocytes prepared from obese- and normal-weight subjects. Insulin binding by such adipocytes was decreased in obesity when the binding activity was expressed per unit of cell surface area. No significant difference from the lean controls was evident, however, when binding was calculated on a per cell basis, indicating that the total receptor content of the cells from the obese subjects was not altered. In addition, the normal difference in the receptor binding affinities previously reported between omental and subcutaneous cells from lean individuals was unaffected by the obese condition. Studies of the molecular weight of the non-reduced insulin receptor in fat cell membranes prepared from pieces of omental and subcutaneous fat demonstrated a major receptor species of 390-425K Mr. In contrast, adipocytes isolated by collagenase treatment of the fat had heterogeneous non-reduced receptor species of Mr 355K, 285K and small amounts of 427K and 182K. Although different non-reduced receptor species were evident depending on the adipocyte receptor preparation (e.g. isolated adipocytes or fat cell membranes), no differences were found between obese and lean controls or between subcutaneous and omental receptors when the appropriate comparisons were made. Upon sulphydryl reduction, all receptor preparations had a major binding subunit of 125K Mr. In conclusion, obesity is characterized by a dilution of the insulin receptor over the adipocyte cell surface in the absence of a change in total cellular content of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Binding and molecular weight properties of the insulin receptor from omental and subcutaneous adipocytes in human obesity. 639 88

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.
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PMID:Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. 820 15

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.
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PMID:Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats. 851 32

Studies with human adipose tissue have demonstrated the presence of key enzymes of fat synthesis. However, long-term regulation of these enzymes has not been reported. To address this issue, we used human adipocytes in primary culture. Human adipose tissue was obtained from abdominal fat of patients undergoing abdominal surgery. Adipocytes were isolated by collagenase digestion and cultured in media supplemented with 1% fetal bovine serum. To evaluate metabolic activity of cultured cells, we assessed the following during the culture: DNA pattern, cell size, glucose consumption and activities for two lipogenic enzymes, fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPDH). Analysis of DNA pattern showed that human adipocytes cultured under the above condition did not undergo cell apoptosis. In addition, no significant change in the cell size occurred during 22 d of culture. Glucose consumption by cultured cells was also constant during the culture and was 60% greater in the presence of 10 nmol/L of insulin. Treatment of cultured human adipocytes with insulin for 3-22 d increased GPDH and FAS activity by 60% and 2.8-fold, respectively, compared to cells cultured without insulin. Furthermore, the increase in FAS activity due to insulin treatment was dose dependent and maximal at 10 nmol/L. Our studies show for the first time that human adipocytes can be maintained viable and metabolically active for 2-3 wk in culture. Interestingly, cultured cells remain responsive to insulin. Therefore, this system will allow further characterization of long-term regulation of lipogenesis in human adipocytes and will be useful for developing pharmacological treatments of obesity.
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PMID:Insulin increases lipogenic enzyme activity in human adipocytes in primary culture. 861 89

Despite improvements in islet isolation techniques, islet transplantation remains unpredictable as a method for reliably rendering human type I diabetic recipients normoglycemic. Advances in immunosuppression to prevent primary nonfunction, to promote engraftment and to prevent rejection should improve success rates. However, factors influencing the isolation process remain incompletely defined. During our experience, the donor's nutritional status as well as other donor characteristics were noted to be associated with islet isolation success. Thus, in this study, we tried to clarify whether the body mass index of the human pancreatic donor affects islet isolation yield and viability. In lean donors we found significantly lower islet yields in comparison with normal and obese donors and a significantly lower islet viability compared to obese donors. Obese donor islets had a significantly higher insulin secretory capacity than lean and normal donor islets. In summary, islet yield and viability were improved selecting pancreata from obese donors associated with a BMI > 24 for islet preparation. We hypothesize that, on the one hand, the increased distribution of fat in pancreata of obese donors possibly can facilitate the release of islets during the collagenase digestion, and, on the other hand, pancreata of obese donors contain more islets than pancreata of lean donors. These data underline the decisive influence of the pancreas donor's body mass index on successful human islet isolation. The body mass index should be noted as a potential predictor of success of islet preparations.
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PMID:Body mass index of pancreatic donors: a decisive factor for human islet isolation. 883 48

Obese and crossbred (X-Bred) pigs were removed from sows at 14 d of age and given ad libitum access to a high-fat, milk-based diet. A subset of pigs fed this diet were killed at 28 and 49 d of age. At 28 d, another subset of pigs was given ad libitum access to a low-fat, grain-based diet and were killed at 31, 35, and 49 d of age (nutritionally weaned for 3, 7, and 21 d, respectively). Dorsal subcutaneous adipose tissue was obtained at death and adipocytes were prepared by incubation with collagenase. A portion of the cells was fixed with osmium to determine size and number; remaining cells were lysed in hypotonic media and centrifuged to yield a crude membrane fraction. The beta-adrenergic receptor (beta-AR) and A1 adenosine receptor (A1R) affinity and number were measured in the membranes by equilibrium saturation ligand binding. Obese pigs had a lower body weight than X-Bred pigs at all ages (P < .05). Obese pigs tended (P for volume > .1 but < .2) to have larger adipocytes than X-Bred pigs. The beta-AR affinity did not differ between obese and X-Bred pigs. There were fewer beta-AR per milligram of membrane protein in obese than in X-Bred pigs at 28 and 49 d of age when fed the high-fat, milk-based diet (P < .01). However, beta-AR number expressed per cell or unit cell surface area did not differ between genetic groups. As pigs of either genetic group continued to be fed the low-fat, grain-based diet, the beta-AR decreased when expressed per milligram of protein or unit cell surface area (P < .05) and tended to decrease when expressed per cell. Obese and X-Bred pigs fed the high-fat, milk-based diet had more beta-AR than respective pigs fed the low-fat, grain-based diet when data were expressed per milligram of protein (P < .01) but not when expressed per cell or unit surface area. The A1R were only detectable in 2 of 16 X-Bred litters but were more developed in adipocytes of obese pigs, being measurable in 8 of 14 litters. The A1R number, expressed per milligram of protein, was lower in obese pigs fed the milk-based diet than in those fed the grain-based diet (P < .05). These findings suggest the decreased beta-AR number after nutritional weaning, or the transition from a high-fat to low-fat diet, may contribute to fat accretion in pigs. Furthermore, the lower number of beta-AR in obese than in X-Bred pigs may contribute to the obesity.
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PMID:Influence of nutritional weaning on porcine adipocyte beta-adrenergic and adenosine A1 receptors. 930 55

Adipose tissue was shown to contain 0.6-1.6 mg of cholesterol per gram wet weight. When expressed per unit of protein or organ mass, fat tissue contains more cholesterol than most other organs or membranes. The cholesterol content of fat tissue increased with the age and weight of the rat. Over 95% of adipose tissue sterols was cholesterol, and most of it was free. In young (150-165 g) rats two-thirds of fat tissue cholesterol was in collagenase-derived adipocytes while in older rats (450-480 g) 90% of fat tissue cholesterol was in adipocytes and the remainder was in stromal-vascular elements. Age-related differences in subcellular cholesterol distribution were also observed. The cholesterol/phospholipid molar ratios of purified plasma membrane fractions from small and large fat cells were identical (0.22-0.25), thus resembling muscle and liver membranes. 7.5 days after intravenous administration of [4-(14)C]cholesterol the specific activity of adipose cholesterol exceeded that of plasma cholesterol. At 28 days the specific activity of adipose and muscle cholesterol exceeded that of plasma three- to fivefold. The t((1/2)) disappearance of adipose tissue cholesterol was approximately 27 days, which is consistent with its function as a slowly turning over storage pool. Thus, fat tissue is a major cholesterol storage organ. This may well account for the marked expansion of the slowly exchangeable cholesterol pool (pool B) observed in obesity.
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PMID:Studies on the compartmentation of lipid in adipose cells. II. Cholesterol accumulation and distribution in adipose tissue components. 970 80


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