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

The ideal hypocaloric diet should reduce body weight, decrease fat more than muscle tissue, and ameliorate insulin sensitivity and lipid levels. The aim of this study was to investigate the effect of three hypocaloric diets with different carbohydrate (CHO) and fat contents on body weight reduction, insulin release and sensitivity, and lipid levels in patients with simple obesity. Twenty-five obese subjects with normal glucose tolerance were randomly allocated to three hypocaloric (800 kcal) diets containing: 60% high complex/high starch and fibre (HC/HSF-CHO) and 20% fat (group 1;11 subjects); 60% high simple/high natural fibre (HS/HNF-CHO) and 20% fat (group 2; 7 subjects); or 20% CHO (L-CHO) and 60% fat (group 3; 7 subjects). The remaining 20% of the diet was protein. In all cases the duration of the diet was 21 days. Before and after the diet, seven subjects from each group underwent a hyperglycemic clamp, and the other four subjects of group 1 underwent a euglycemic-hyperinsulinemic clamp, combined with a glucose turnover study. A similar decrease in body weight, fat-free mass, fat mass, total cholesterol, LDL cholesterol and apo B levels was observed in the three groups. The M/I ratio during hyperglycemic and euglycemic-hyperinsulinemic clamp and the glucose turnover rate during euglycemic-hyperinsulinemic clamp significantly decreased, and FFA levels significantly increased only after the HC/HSF-CHO diet. HDL cholesterol and apo A1 significantly increased only during the HS/HNF-CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin sensitivity and lipid levels in obese subjects after slimming diets with different complex and simple carbohydrate content. 839 72

It has been shown that visceral obesity is associated with an increased incidence of hyperinsulinemia. In such a condition, hyperinsulinemia could be due to an increased lipolytic activity of omental adipose tissue (AT), through an enhanced portal flux of FFA. The purpose of our study was to evaluate the lipolytic activity of omental and epigastric AT obtained from morbid obese patients either with prevalently visceral or subcutaneous abdominal fat accumulation, evaluated by computerized tomography. The relationship between plasma insulin values and in vitro lipolytic activity in both tissues was studied. Thirteen visceral (VO) and 13 subcutaneous (SO) obese patients, matched for sex and body mass index, undergoing vertical banded gastroplasty, were studied. Before surgery, in each patient an OGTT was performed. During surgery, samples of epigastric subcutaneous and omental AT were obtained for evaluation of fat cell weight (FCW) and basal, noradrenaline 10(-5)M and isoprenaline 10(-5) M induced lipolytic activities. No significant differences in basal lipolysis were found between the two types of obesity, both in omental and in epigastric AT. In omental AT, a higher noradrenaline and isoprenaline induced lipolysis was observed in VO than in SO. Isoprenaline induced lipolysis of omental AT (expressed per cell surface area) correlated directly with FCW. VO patients showed plasma insulin values after OGTT significantly higher than SO patients. In the whole group of patients, independently from fat distribution, significant correlations were found between the incremental areas of the plasma insulin curve during OGTT and the noradrenaline an isoprenaline induced lipolytic activities both in omental and epigastric adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Omental and epigastric adipose tissue lipolytic activity in human obesity. Effect of abdominal fat distribution and relationship with hyperinsulinemia. 840 22

Obesity is a risk factor of atherosclerosis. The TG content of a fat cell is determined by the balance of lipogenesis from plasma FFA and glucose and lipolysis by hormone-sensitive lipase (HSL). Plasma FFA is produced by TG lipolysis by lipoprotein lipase (LPL). Insulin stimulates LPL activity and inhibits HSL activity. Therefore, hyperinsulinemia stimulates TG accumulation in fat cells. Insulin also stimulates fat cell proliferation. Hyperinsulinemia is a major factor for obesity. Portal FFA stimulates VLDL synthesis and gluconeogenesis and inhibits insulin degradation in the liver. Therefore, visceral obesity is important as a risk factor of atherosclerosis. However the increase of total adipose tissue mass is more important for blood pressure and cardiac performance.
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PMID:[Atherosclerotic and hemodynamic effects of obesity]. 841 92

Epidemiologic studies demonstrate an association between increased waist to hip ratio ([WHR] android obesity, central obesity) and diabetes mellitus in man. To study the relative insulin sensitivity of splanchnic versus peripheral adipose tissue, portal vein catheterization via the collapsed umbilical vein was performed in 14 morbidly obese subjects at the time of surgery. Catheters were also placed in a peripheral artery and antecubital vein such that simultaneous arterio-venous (A-V) differences (glycerol, free fatty acids [FFA], and lactate) could be determined. After two baseline samples obtained 3 minutes apart, 25 g intravenous (i.v.) glucose (14 subjects) was administered over a 2-minute period, with samples being obtained every 5 minutes for 30 additional minutes. Arterial plasma glycerol levels decreased from 173.9 +/- 17.4 mumol/L at baseline to 89.1 +/- 7.6 mumol/L at 30 minutes (P < .01). Peripheral and splanchnic A-V glycerol differences were similar at baseline, but within 10 minutes after glucose administration the difference across the splanchnic area decreased by 52% and remained significantly less than that across the periphery (P < .01). Despite a 49% decrease in arterial plasma glycerol level, plasma FFA level decreased only 18.3% over the 30-minute period (942 +/- 74.8 to 770.0 +/- 76 mumol/L, NS). These studies in morbidly obese man (glycerol data) indicate a greater insulin sensitivity of splanchnic adipose tissue than of peripheral adipose tissue. Thus hypertrophy of fat in the splanchnic area might be an expected consequence of the hyperinsulinemia associated with insulin-resistant states.
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PMID:Insulin sensitivity of splanchnic and peripheral adipose tissue in vivo in morbidly obese man. 841 75

The effects of short-term hyperinsulinemia on the production of both VLDL triglyceride and VLDL apoB were determined semiquantitatively before and during a 6-h euglycemic hyperinsulinemic clamp (40 mU.m-2 x min-1) in 17 women (8 chronically hyperinsulinemic obese, BMI = 35.7 kg/m2; 9 normal weight, BMI = 22.5 kg/m2). During acute hyperinsulinemia, plasma FFA decreased by approximately 95% within 1 h in both groups. VLDL triglyceride production decreased 66% in the control subjects (P = 0.0003) and 67% in obese subjects (P = 0.0003). ApoB production decreased 53% in control subjects (P = 0.03) but only 8% in obese (NS). Plasma triglycerides decreased by 40% from baseline in control subjects (P < 0.0001) but only by 10% in obese subjects (P = NS). Despite the similar decrease in triglyceride and apoB production in control subjects, VLDL particle size (triglyceride-to-apoB ratio) decreased with hyperinsulinemia (P = 0.003). In obese subjects, despite a decrease in triglyceride production similar to that in control subjects but no change in apoB production, VLDL size did not change appreciably. Acute hyperinsulinemia in humans: 1) suppresses plasma FFA equally in control and obese subjects at this high dose of insulin; 2) inhibits VLDL triglyceride production equally in control and obese subjects, perhaps secondary to the decrease in FFA; 3) inhibits VLDL apoB production in control but less so in obese subjects, suggesting that obese subjects may be resistant to this effect of insulin; 4) decreases plasma triglyceride and VLDL particle size in control subjects, reflecting either stimulation of LPL activity or a greater relative decrease in triglyceride to apoB production; and 5) does not decrease plasma triglyceride or VLDL size in obese subjects to the same extent as it does in control subjects. Thus, the insulin resistance of obesity affects some but not all aspects of VLDL metabolism.
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PMID:Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. 849 7

Obesity is associated with dyslipidaemia and increased morbidity and mortality from premature atherosclerosis and diabetes mellitus. Particularly, hypertriglyceridaemia is a characteristic finding in patients with obesity. In addition, the elevated levels of triglycerides may be an important risk factor for development of the obesity-related complications. Lipoprotein lipase activity in skeletal muscle tissue (mLPL) has previously been found to be an important factor regulating the concentration of serum triglycerides. To describe the relationship between mLPL, triglycerides and fatness/fat distribution in more detail we have investigated these parameters under basal conditions and during insulin stimulation in 20 obese females. During hyperinsulinaemia (204 microU ml-1) for 4 h the mLPL activity decreased from 528 +/- 52 nmol FFA g-1 to 412 +/- 44 (P < 0.001). Basal mLPL was negatively correlated with serum triglycerides (r = -0.48, P < 0.05) and positively correlated with HDL-cholesterol (r = 0.58, P < 0.01). Employing multiple variance analysis it was found that both BMI and WHR were negatively correlated to mLPL, however, the impaired lipid profile (high triglyceride, low HDL-cholesterol, high FFA) could only be related to BMI and not to WHR in these obese females. However, reduced insulin-action (insulin resistance) was closely related to abdominal fatness determined by WHR both in relation to the insulin-effect on mLPL as well as for the insulin-effect on whole-body glucose metabolism (clamp-study).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females. 850 May 14

Plasminogen activator inhibitor 1 (PAI-1) levels are elevated in obese insulin-resistant subjects. However the mechanism underlying increased PAI-1 levels is unknown. To determine the impact of diabetes on PAI-1 levels and its possible relationship to insulin resistance, hyperinsulinemic euglycemic clamp studies were performed in nine lean control subjects, nine non-diabetic obese subjects and eight obese patients with NIDDM. Fasting plasma PAI-1 levels were 4.0 to 4.7 fold higher in the two obese groups than in the control group. During the 40 mU/m2 x min insulin infusion, suppression of FFA concentration was correlated with fasting plasma PAI-1 levels in both obese non-diabetic and obese NIDDM subjects. It is concluded that (1) obesity rather than diabetes itself plays a major role for the increased PAI-1 levels in NIDDM; (2) resistance to the antilipolytic effect of insulin, resulting in increased FFA concentrations, may participate in producing elevated PAI-1 levels in android obese subjects.
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PMID:Are free fatty acids related to plasma plasminogen activator inhibitor 1 in android obesity? 858 88

Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle-specific insulin resistance can contribute to the development of obesity; and 3) a "pure" defect in insulin-mediated muscle glucose disposal is sufficient to result in impaired glucose tolerance and other features of the insulin resistance syndrome, including hyperinsulinemia and dyslipidemia.
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PMID:Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, and dyslipidemia. 864 Nov 92

The aim of this study was to investigate whether the EcoRI polymorphism of the apolipoprotein B (apoB) gene influences the relationships between features of the insulin resistance syndrome and the dense LDL phenotype and apoB concentrations. A sample of 65 men was divided into two groups on the basis of the EcoRI genotype. Forty-four subjects were (+/+) homozygotes for the presence of the EcoRI restriction site that is associated with a glutamic acid at codon 4154. Twenty-one men were (+/-) heterozygotes for the absence of the restriction site resulting from a glutamic acid to a lysine substitution at codon 4154. In the (+/-) group, fasting plasma FFA levels were positively correlated with plasma apoB, LDL-apoB, and the LDL particle score that was calculated from the migration distances of LDL subspecies and their relative band intensities, reflecting the proportion of small dense LDL particles. However, these associations were not found among (+/+) subjects. The two genotypic groups were further divided into two subgroups on the basis of fasting FFA concentrations, and the LDL particle score and the LDL-apoB levels were compared. High FFA levels were associated with a higher proportion of small dense LDL particles, as reflected by a higher mean LDL particle score, irrespective of the genotype. However, the apoB-EcoRI polymorphism appeared to influence the association between high FFA levels and LDL-apoB concentrations because (+/-) heterozygotes with high FFA levels had higher LDL-apoB concentrations than (+/-) heterozygotes with low FFA levels. In addition, the integrated area under the curve of plasma insulin concentrations, measured in response to a 75-g oral glucose challenge, and the amount of visceral adipose tissue, measured by computed tomography, were positively associated with the LDL particle score only in (+/-) heterozygotes. When subjects were divided on the basis of insulin area (low vs. high) or visceral adipose tissue (low vs. high), (+/-) heterozygotes with high insulin area or with high levels of visceral adipose tissue had a higher mean LDL particle score than (+/-) heterozygotes with low insulin area or low visceral adipose tissue. However, among (+/+) homozygotes, low or high levels of insulin or visceral adipose tissue could not discriminate between men with large or small LDL particles. Therefore, (+/-) heterozygotes may be more susceptible to develop the dense LDL phenotype in presence of hyperinsulinemia and visceral obesity. Results of the present study suggest that the apoB-EcoRI polymorphism may exacerbate the alterations in the LDL particle (size and concentration) found among visceral obese-hyperinsulinemic men.
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PMID:The apoB-100 gene EcoRI polymorphism influences the relationship between features of the insulin resistance syndrome and the hyper-apoB and dense LDL phenotype in men. 882 78

In vivo FFA block basal and stimulated GH secretion and have been implicated in the pathogenesis of the altered GH secretion present in obesity and Cushing's syndrome. Although a direct action on the somatotroph cell has been postulated, the FFA mechanism of action is unknown. The main biological target for FFA action is the cellular membrane, and it has been shown that these metabolites can block the activity of a number of plasma membrane pumps, channels, and receptor systems. In the present work, it was observed using different types of pituitary cells (GH3, GH4C1, and rat pituitary primary cultures) that cis-unsaturated fatty acids, such as oleic, 1) do not perturb TRH binding or the homologous desensitization of the TRH receptor; 2) inhibit TRH-induced inositol 1,4,5-trisphosphate/diacylglycerol generation, probably by a direct perturbation of phospholipase C; 3) reduce the TRH-induced intracellular Ca2+ redistribution and the ensuing changes in membrane potential; 4) completely inhibit the [Ca2+]i rise due to the TRH-induced opening of voltage-gated Ca2+ channels; and 5) abolish the TRH-induced Ca2+ efflux through plasma membrane Ca2+ pumps. These results suggest that cis-unsaturated FFA such as oleic acid selectively perturb the function of integral membrane proteins such as enzymes, channels, and pumps without perturbing the binding of ligands to receptors.
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PMID:cis-unsaturated free fatty acids block growth hormone and prolactin secretion in thyrotropin-releasing hormone-stimulated GH3 cells by perturbing the function of plasma membrane integral proteins. 897 13


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