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)

Small changes in lipogenic enzyme activity induced by dietary fats of different composition may, over the long term, have significant impact on the development of obesity. We have investigated the effect of high fat diets (45% of calories as fat) on abundance of mRNA encoding fatty acid synthetase (FAS) and glycerophosphate dehydrogenase (GPDH) in male Sprague-Dawley rats. When caloric intake was equal, the relative amount of hepatic FAS mRNA was greater in rats fed a saturated compared to a polyunsaturated fat diet. This difference could not be attributed to diet-induced changes in plasma insulin concentration. However, both fat diets suppressed hepatic FAS mRNA compared to a sucrose diet. Close correlation between FAS specific activity and the relative amount of mRNA suggested that regulation was mainly at a pre-translational level. Adipose tissue FAS mRNA was suppressed by the two fat diets equally while GPDH mRNA was unaffected by dietary composition. Retroperitoneal fat pads were significantly larger in rats fed saturated compared to those fed polyunsaturated fat for 26 weeks. We concluded that dietary saturated fats fail to suppress hepatic de novo lipogenesis as effectively as polyunsaturated fats, which may have implications for the prevention of obesity in humans.
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PMID:Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat. 219 Oct 66

The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid-responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat.
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PMID:Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats. 220 81

Adipsin is a serine protease with complement factor D activity that is synthesized by adipocytes and secreted into the blood stream. Expression of adipsin is deficient in models of genetic (ob/ob, db/db) and acquired (monosodium glutamate-lesioned) obesity, but the cellular mechanisms responsible for this deficiency are unknown. Because hyperinsulinemia is frequently associated with obesity, we evaluated the effects of this hormone and insulin-like growth factor 1 (IGF-1) on adipsin secretion and adipsin messenger RNA (mRNA) levels in 3T3-F442A adipocytes. In the present study, we report that in fully differentiated adipocytes (after 11 days post confluence), insulin exposure progressively decreases adipsin secretion by 40%, 67%, and 78% after 2, 4, and 6 days of treatment. The inhibition of adipsin secretion by insulin is the result of a corresponding decrease in adipsin mRNA and is specific since two other differentiation-dependent fat cell mRNAs encoding aP2 (a fatty acid binding protein) and glycerophosphate dehydrogenase (GPD), are unaffected. Insulin suppresses adipsin gene expression via high affinity insulin receptors, because physiological levels of insulin produce this effect, and dose-response curves for insulin stimulation of 2-deoxyglucose uptake and glucose utilization are similar to insulin's effect on adipsin. In contrast, insulin when present during days 1-8 post confluence (during differentiation) markedly increases adipsin secretion and adipsin mRNA levels. This stimulation is due to the ability of insulin to accelerate differentiation as evidenced by corresponding increases in aP2 and GPD mRNAs as well. Insulin and IGF-1 are equipotent in this effect, suggesting that both insulin and IGF-1 receptors can mediate this response. In summary, during the differentiation of 3T3-F442A adipocytes, insulin stimulates adipsin gene expression by accelerating differentiation. As the cells become mature adipocytes, they acquire some differentiation-dependent factor, which couples insulin receptor stimulation to inhibition of adipsin gene expression. This model should aid our search for the molecular links between insulin receptor stimulation and altered gene expression.
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PMID:Differentiation dependent biphasic regulation of adipsin gene expression by insulin and insulin-like growth factor-1 in 3T3-F442A adipocytes. 224 32

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

The potential of plasma to stimulate differentiation and lipid filling of adipose precursors in primary culture was investigated in the groups of genetically obese Zucker rats (fafa) and their lean littermates (FaFa). The effect of age, feeding status and possible role of growth hormone in the process of adipogenesis was also studied. Differences in lipid-filling activity of the tested plasma samples were much more dependent on age than the genotype of plasma donors were. The plasma taken from the oldest (20-week-old) rats stimulated the accumulation of triglycerides in the cells to significantly higher levels than the plasma from other rats. The influence of the feeding status on the lipid-filling activity of plasma was not significant. The differentiation potential of plasma in terms of the stimulation of glycerophosphate dehydrogenase activity measured in adipocyte precursors was 30-50% higher when the culture medium contained plasma from obese rats. Furthermore, glycerophosphate dehydrogenase activity in the growing cells declined with age and tended to be higher in the presence of plasma from fed rats. It was the growth hormone that was in a considerable degree responsible for the differentiation potential of Zucker rat plasma. This effect of growth hormone seemed to be less dependent on fafa genotype. It is, therefore, suggested that in addition to growth hormone, other factors in the plasma of genetically obese Zucker rats might be important in the development of obesity in this rat strain.
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PMID:Adipogenic activity in the plasma of genetically obese Zucker rats. 248 49

The potential was examined for insulin, growth hormone and insulin-like growth factor (IGF-1) alone or in combinations to stimulate glycerophosphate dehydrogenase (GPDH) activity, a sensitive marker of differentiation of adipose precursor cells in primary culture. Insulin, but not growth hormone or IGF-1, stimulated GPDH in the presence of fetal calf serum and cat serum. The content of growth hormone in adult rat heparinised plasma seemed, however, important for such stimulation, but was also dependent on feeding status of the plasma donor, and was abolished by hypophysectomy of the cell donor. GPDH activity was then analysed in heparinised plasma in the over-night fasting state in humans to examine a potential influence of age, obesity and pregnancy. In comparison with non-obese adults, GPDH-stimulatory activity was higher in plasma from infants and small children. A similar trend was seen in plasma from teenagers. This activity was probably partly dependent on growth hormone, because this increase of activity could be inhibited by excess of anti-human growth hormone antiserum. Obesity in adulthood or among teenagers was not associated with any difference in plasma activity to stimulate cellular differentiation, and plasma from women during late pregnancy had a low stimulating capacity. Simultaneous analyses of the potential of plasma to stimulate lipid accumulation in adipose precursor cells was proportional to the triglyceride concentration. Overall, the inhibitory effect of antihuman growth hormone antiserum on the differentiating capacity of human plasma was small or non-existing. It is therefore suggested that in human plasma, factors other than growth hormone might be important for the differentiation of adipocyte precursor cells.
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PMID:Effects of age, obesity and growth-hormone on adipogenic activity in human plasma. 331 49

The potential of plasma from obese and non-obese subjects to stimulate the formation of new adipocytes was studied by assays in rat adipose precursor cells in primary culture. Adipogenic activity was followed in terms of rate of lipid filling, analysed by determination of triglyceride contents per unit protein, stimulation of multiplication, measured as rate of incorporation of labelled thymidine into DNA, and stimulation of differentiation, followed as an increase in glycerophosphate dehydrogenase activity. Plasma from obese subjects contained an excess of activity stimulating lipid filling, closely associated to the recent body weight histories with increased activity with a recent increase of body weight and vice versa. There was also a strong association with plasma concentration of triglyceride. The importance of the latter was demonstrated by acute feeding experiments with triglyceride, as well as by addition of isolated very-low-density lipoprotein and chylomicron fractions which caused increases of lipid filling activity closely in parallel to triglyceride contents of the culture medium. Specific stimulatory properties of plasma from weight-increasing obese subjects on adipose precursor cell multiplication and differentiation were not found. It was suggested that human obesity with an increased number of adipocytes is not characterized by elevated circulating specific stimulatory factors of new fat cell formation. Such factors are present in excess in both non-obese and obese subjects. It was hypothesized that the elevated lipid filling capacity in obese subjects might modify local inhibitory factors of adipocyte formation.
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PMID:Adipogenic activity in human plasma. Effects of feeding state and obesity. 377 Oct 91

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

Body weight, obesity and liver weights of male raccoon dogs fed diets of various energy content were higher than those of females. With increasing body weight and obesity the liver weight and glucose-6-phosphate dehydrogenase (G-6-PD) decreased significantly in both sexes. The liver weight correlated very positively with the G-6-PD activity. The alpha-glycerophosphate dehydrogenase (alpha-GPD) correlated with the liver weight only in females.
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PMID:Lipogenic hepatic enzyme activity of raccoon dogs (Nyctereutes procyonoides) fed various diets. 396 89

The stroma vascular fraction of adipose tissue partly consists of adipose precursor cells which can convert into adipocytes in vitro. The aim of this study was to investigate the possible contribution of cells from the stroma vascular compartment to the initiation of obesity induced by overfeeding during the early neonatal weeks in rats. Overfeeding during the suckling period was obtained by reducing the litter size. The inguinal adipose tissue of overfed rats raised in litters of 4 pups each was overdeveloped compared to that of controls raised in litters of 8 pups each, and the difference between the two groups became significant as early as 10 days of age. At this age, adipose tissue enlargement was only due to adipocyte hypertrophy; afterwards, hyperplasia of the mature fat cells contributed to the overdevelopment of adipose tissue in 15-day old overfed rats. The cell number in the stroma vascular fraction increased in the overfed group as early as 10 days of age and thus preceded the onset of mature fat cell hyperplasia. The developmental pattern of lipoprotein lipase, glycerol-3-phosphate dehydrogenase, glycerol-acyl-transferase and acyl-CoA ligase activities in stromal cells did not depend on litter size, but specific enzyme activities wee increased in 10-day old overfed rats compared to the controls. These results indicate that early overfeeding induced cell proliferation in the stroma vascular compartment and also induced the enzyme activities involved in adipose conversion to increase in these cells. This strongly suggests that precursor cell differentiation was greater in overfed rats than in control rats.
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PMID:[Role of adipocyte precursors in the initiation of nutritional obesity before weaning]. 399 88


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