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

Obesity in obese-hyperglycaemic mouse is associated with an increase in number and size of adipocytes. Adipocytes from the obese mouse showed increased incorporation of [14C]acetate and[14C]glucose into triacylglycerol. This increased capacity of triacylglycerol formation was correlated with increased activities of various triacylglycerol-forming enzymes measured in the microsomal fraction of adipose tissue from obese mice. Microsomal fractions from lean and obese mice contained sn-glycerol 3-phosphate acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase. Phosphatidate phosphohydrolase was also detected in the soluble fraction. In the presence of Mg2+, the phosphatidate phsophohydrolase from the soluble and the microsomal fractions was active towards membrane-bound phosphatidate. Among the three enzymes studied here, the increase in Mg2+-dependent phosphatidate phosphohydrolase was most prominent in adipose tissue of obese mice.
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PMID:Triacylglycerol biosynthesis in the adipose tissue of the obese-hyperglycaemic mouse. 18 34

It is well known that abnormality of the coagulation-fibrinolytic system and serum lipids plays an important role in the development of thrombi and atherosclerotic disease. In the present study, the correlation between the activity of tissue plasminogen activator (TPA), the levels of tissue plasminogen activator inhibitor (PAI-1) and serum lipids (TC, TG, beta-Lp, HDLC, LDLC and apolipoproteins) were studied in 102 healthy subjects. The activity of TPA showed negative correlation with the obesity rate (r = 0.21, p less than 0.05) but levels of PAI-1 antigen showed a positive correlation with the obesity rate (r = 0.182, p less than 0.1). The activity of TPA showed no correlation with serum lipids including apolipoproteins, while the levels of PAI-1 antigen showed a positive correlation between TG and beta-Lp (r = 0.292, p less than 0.01, r = 0.211, p less than 0.05). The levels of PAI-1 antigen showed a negative correlation with HDLC (r = -0.286, p less than 0.01). These results indicate that TPA and PAI-1 play an important role in the development of thrombotic disease and atherosclerotic disease.
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PMID:[The correlation between the activity of tissue plasminogen activator (TPA), levels of tissue plasminogen activator inhibitor (PAI-1) antigen and serum lipids in healthy subjects]. 212 38

The effects of obesity and sex on hepatic insulin metabolism were evaluated in the SHR/Mcc-cp rat. During in situ liver perfusion, insulin clearance rate (CLR) expressed per gram of liver tissue was reduced by 58 and 68% in obese females and males, respectively, compared with lean controls. Male sex resulted in CLR reductions of 46% in lean and 59% in obese animals. Obesity resulted in 50% reduction of insulin-receptor binding to isolated hepatocytes. In both lean and obese animals, male sex also resulted in a decrease of approximately 34% in insulin binding. Scatchard plots indicated that the reduction in insulin binding was primarily due to a decrease in number of cell surface receptors. Receptor-mediated insulin degradation was 40% less in obese than lean animals. Male sex also resulted in 27% less insulin degradation relative to females. Receptor-mediated insulin partitioning between four compartments (cell surface bound, internalized and/or cryptic, degraded, and dissociated or released intact), expressed as a percentage of the initial membrane-bound hormone, did not differ between the animal groups. Thus, male sex and obesity are independently and additively associated with a reduction in hepatic insulin clearance and a decrease in the number of cell surface insulin receptors with a proportional decrease insulin compartmentalization and degradation. This mechanism may partly account for the synergistic effects of male sex and obesity on the degree of hyperinsulinemia and insulin resistance and the predisposition to diabetes.
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PMID:Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat. 219 85

In an attempt to determine the mechanism of insulin resistance in the presence of obesity, we examined effects of insulin on insulin-sensitive phosphodiesterase (PDE) in spontaneously diabetic KK mice. Isolated fat cells prepared from epididymal adipose tissue were incubated, with or without insulin, for 10 min. In the case of subcellular fractionation, only membrane-bound PDE was activated by insulin, as was noted in the case of rat fat cells. The specific activity was decreased in KK mice compared with control C57BL/6 mice. The dose-response curve, expressed as a percent of the maximal insulin effect, shifted to the right and the increase of ED50 indicated a decreased insulin sensitivity in the KK mice. The maximal insulin effect did not change, either when expressed as a percent of the basal enzyme activity or when expressed on a per cell basis. Specific binding of [125I]-insulin in fat cells increased in KK mice and curvilinear Scatchard plots showed an increase of the high-affinity sites. These data indicate that impairment of PDE activation in fat cells of KK mice relates to postreceptor defects and the uncoupling may result in a decreased sensitivity.
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PMID:Insulin resistance of fat cells from spontaneously diabetic KK mice. Analysis of insulin-sensitive phosphodiesterase. 299 83

Recent data suggest that the protection against ischemic heart disease afforded by high density lipoprotein (HDL) cholesterol (C) may be concentrated in the HDL2 subfraction. To examine the behavioral correlates of the HDL subfractions, we recalled 33 men and 17 women of a random sample from the Pacific Northwest Bell Telephone Company Health Survey. Adiposity and very low density lipoprotein (VLDL) triglyceride were negatively correlated with HDL2C. Smoking was not correlated with HDL2C, but was negatively correlated with HDL3C (men, rs = -0.635, p = 0.001; women, rs = -0.534, p = 0.014); this relationship was independent of alcohol consumption, adiposity, and VLDL triglyceride. Alcohol consumption was also more strongly related to HDL3C (men, rs = 0.248, p = 0.082; women, rs = 0.586, p = 0.007). Lecithin cholesterol acyltransferase (LCAT) mass was negatively related with HDL2C, but was positively correlated with HDL3C and apolipoprotein A-II. Smoking was negatively correlated with LCAT mass. Since it is believed that HDL3C is not associated with the risk of ischemic heart disease and since both smoking and alcohol consumption may mainly affect HDL3C, the current study suggests that the increase in risk of ischemic heart disease with smoking and the possible decrease with alcohol consumption may be mediated through mechanisms other than their effects on HDLC.
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PMID:Epidemiological correlates of high density lipoprotein subfractions, apolipoproteins A-I, A-II, and D, and lecithin cholesterol acyltransferase. Effects of smoking, alcohol, and adiposity. 391 1

Recent advances in the understanding of circulating growth hormone binding proteins (GHBP) are reviewed. The high affinity GHBP represents the ectodomain of the GH receptor (GHR); it is either cleaved from membrane-bound GHRs (man, rabbit) or derived from an alternatively spliced GHR mRNA (rodents). Another circulating GHBP, of low affinity and not GHR-related, is only partially characterized. The GHBPs complex about half of the GH in human plasma. They act as a buffer regulating free and bound GH, prolong GH half-life, and modulate GH bioactivity through competition with GHRs for ligand. The plasma levels of both GHBPs are developmentally upregulated during childhood and remain relatively constant thereafter. Different species vary in their regulation of GHBP, with sexual dimorphism and large pregnancy-related changes in some but not all species. A variety of conditions associated with altered GH responsivity (resistance or hypersensitivity) are attended by altered levels of the high affinity GHBP. Generally, GH resistance is characterized by decreased GHBP levels, and the converse is true in GH hypersensitivity such as in obesity. It has been postulated that the plasma GHBP level reflects tissue concentrations of the GHR, but this remains to be proven. The high affinity GHBP appears to be positively, though imperfectly, linked to GH action. Soluble receptor isoforms analogous to the GHBP have been demonstrated for several members of the cytokine receptor family to which the GHR belongs. The ultimate biological role of these circulating receptor ectodomains remains to be fully defined.
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PMID:Growth hormone binding to a circulating receptor fragment--the concept of receptor shedding and receptor splicing. 762 Nov

Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 Zulus (age range 16-69 years) were studied. The prevalence of CHD was 2.4%. The prevalence percentage of selected risk factors were: hypertension (SBP > or = 140 mmHg and/or a DBP > or = 90 mmHg) was 28%, males 31.9%, females 25.4%; protective levels of high density lipoprotein cholesterol/total cholesterol (HDLC/TC) (> or = 20%) were 81.3%; diabetes, males 4.9%, females 2.9%; smoking > or = ten cigarettes per day, males 28.1%, females 3.4%; obesity, males 3.7%, females 22.6%. We have found the Minnesota Coding System for ECG changes of CHD and Rose questionnaire to be unreliable for eliciting CHD in Blacks. Hypercholesterolaemia is less common and this may explain the low incidence of CHD in Blacks. Epidemics of CHD as seen in the Indian, 'mixed' and white South Africans can still be prevented in the black population but preventive measures must be instituted rapidly.
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PMID:Study of risk factors leading to coronary heart disease in urban Zulus. 811 40

The lipid composition of cellular membranes is regulated to maintain membrane fluidity. A key enzyme involved in this process is the membrane-bound stearoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids. A proper ratio of saturated to monounsaturated fatty acids contributes to membrane fluidity. Alterations in this ratio have been implicated in various disease states including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, hypertension, neurological diseases, immune disorders, and cancer. The regulation of stearoyl-CoA desaturase is therefore of considerable physiological importance and its activity is sensitive to dietary changes, hormonal imbalance, developmental processes, temperature changes, metals, alcohol, peroxisomal proliferators, and phenolic compounds. Two mouse and rat SCD genes (SCD1 and SCD2) and a single human SCD gene have been cloned and characterized. In the past several years we have studied the dietary influences on the genetic expression of the mouse stearoyl-CoA desaturase. The expression of the mouse SCD genes is regulated by polyunsaturated fatty acids and cholesterol at the levels of transcription and mRNA stability. Promoter elements that are responsible for the polyunsaturated fatty acid repression colocalize with the promoter elements for SREBP-mediated regulation of the SCD genes. It is the goal of this review to provide an overview of the genetic regulation of the stearoyl-CoA desaturase in response to dietary polyunsaturated fatty acids and cholesterol.
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PMID:Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. 1048 2

Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.
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PMID:Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro. 1049 4

Examination of random insertional mutations in transgenic animals harbouring an abnormal phenotype contributes to the discovery of new genes and/or the understanding of already known genes. Here we describe a transgenic mouse line showing early-onset obesity as consequence of the transgene insertion. Molecular genetic analysis revealed a partial deletion of the leptin receptor (Lepr, Ob-R) gene including the coding sequences downstream of exon 17'. This defect prevents the expression of all described membrane-bound isoforms of Ob-R except for isoform Ob-Rc in the homozygous transgenic animals. Thus, this mouse model might be useful for the investigation of the function of the short Ob-R isoforms.
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PMID:Partial leptin receptor gene deletion in transgenic mice prevents expression of the membrane-bound isoforms except for Ob-Rc. 1070 82


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