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

In this brief overview the central role of the endocrine aberrations of visceral obesity has been emphasized. Indeed, it may provide not only a background to the pronounced insulin resistance seen in that condition, but also explain why lipid accumulates in visceral depots. It is possible that this lipid accumulation actually amplifies and widens the metabolic derangements via hepatic mechanisms induced by an excess of FFA in the portal vein. This chain of events has not been conclusively established. There is, however, considerable experimental support for several crucial parts of it, providing an interesting hypothesis for further work. Intervention studies will probably be of value for further evaluation and these are already being carried out.
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PMID:Metabolic abnormalities in visceral obesity. 157 59

The effects of FFA on hepatic insulin clearance were studied in the in situ perfused rat liver. Clearance decreased with increasing body weight (age) of the rats. When FFA were added to the perfusate a 40% reduction of hepatic removal of insulin was found over the normal, physiological range (less than 1,000 mumol/liter), less pronounced in heavier rats. When perfusion was started with high concentrations of FFA, inhibition was rapidly reversible, a phenomenon again blunted in heavier rats. In contrast to FFA, different glucose concentrations in the perfusate did not affect the hepatic insulin uptake in the presence of FFA within physiological concentrations. Thus, hepatic clearance of insulin is proportional to rat weight (age) and portal FFA concentrations. Other studies have recently shown that fatty acids inhibit insulin binding, degradation, and function in isolated rat hepatocytes, and that hepatic clearance is inversely dependent on hepatic triglyceride concentrations, both inhibitions reversible by prevention of fatty acid oxidation. It is suggested that the diminished hepatic clearance of insulin in heavier (older) rats is at least partly due to their relative obesity and increased hepatic triglyceride contents. This effect as well as that of portal FFA is probably mediated via fatty acid oxidation in the liver. This mechanism may have implications for the regulation of hepatic metabolism, and peripheral insulin concentrations.
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PMID:Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. 175 63

We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than 0.001) with post-glucose insulin concentrations in the relatives only.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationships of obesity indices to serum insulin and lipoproteins in relatives of black patients with noninsulin-dependent diabetes mellitus (NIDDM). 189 21

Cushing's syndrome has been recently compared to visceral-type obesity, since it is characterised by the accumulation of adipose tissue at a deep abdominal site, to the detriment of the subcutaneous adipose panniculus, and is associated with insulin-resistance and hyperlipemia. The aim of the present study was to evaluate the influence of glucocorticoid hormones on lipolytic activity (index of FFA mobilisation) and on lipoproteinlipase (LPL) activity (an index of the accumulation of triglycerides) in subcutaneous and perirenal adipose tissue in order to clarify the mechanisms involved in this type of accumulation in Cushing's syndrome. Five patients (4 F and 1 M) were included in the study, mean age 27.8 +/- 3.7 years and BMI 21.3 +/- 1.2 kg/m2; patients were hospitalised in the 2nd Surgical Clinic at the University of Padua and underwent surgery for secondary corticosurrenal hyperplasia with ACTH secreting hypophysial adenoma. Lipolytic activity in subcutaneous adipose tissue in these patients was significantly lower (p less than 0.05) than in control subjects, in particular after noradrenalin stimulation (p less than 0.01). No significant difference was observed when lipolytic activity in subcutaneous adipose tissue was compared to that one in perirenal tissue. LPL activity in subcutaneous adipose tissue did not reveal statistically significant differences compared to control subjects, although values were lower. A further decrease in LPL activity, which was not however significant, was observed in perirenal tissue in comparison to subcutaneous tissues in the same patients. The mean weight of adipocytes (ug) was slightly lower in subcutaneous adipose tissue compared to control subjects and even lower in perineal tissue in comparison to the subcutis in the same patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lipolytic and lipoprotein lipase activity of subcutaneous and visceral adipose tissue in Cushing's syndrome]. 210 37

It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulin-stimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800-1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = -0.43; P less than 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = -0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin-stimulated glucose uptake in the patients we studied.
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PMID:Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. 222 87

The effect of obesity on the serum protein binding of theophylline was investigated in man and rat along with other ancillary variables such as dialysis time, theophylline concentration, albumin concentration, and fatty acid type and concentration. The percent binding of theophylline first increased with dialysis time, reached equilibrium over 2 to 6 h, then diminished. This decrease was not due to instability of theophylline. Theophylline binding was linear over a concentration range of 15 to 150 micrograms ml-1. A similar degree of binding was found in normal humans (44.4 +/- 1.0%) and rats (41.5 +/- 0.5%). The binding ratio (bound/free) of theophylline was proportional to the albumin concentration (1 to 5%) and yielded a binding parameter (NK) of 1.47 x 10(-3) M-1. Over a normal physiological range, individual and mixed fatty acids had minimal effects on theophylline binding to albumin. However, binding significantly decreased as fatty acid (FFA) concentrations increased. The magnitude of the effect appeared to parallel the carbon chain number of the fatty acid. Theophylline binding in obese subjects decreased to a mean (SD) of 35.8 +/- 8.0 per cent compared to 43.0 +/- 6.1 per cent in normal subjects (p less than 0.05). Similar decreases were found in normal versus obese rats and in the saliva: serum ratio following theophylline administration to normal and obese human subjects. Obesity causes a moderate decrease in serum binding of theophylline which may be attributed to increased FFA rather than in vitro artifacts.
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PMID:Effects of obesity and ancillary variables (dialysis time, drug, albumin, and fatty acid concentrations) on theophylline serum protein binding. 261 56

Sustained elevations of plasma glucose and insulin concentrations follow intense (80% maximum oxygen uptake) exercise performed in the postabsorptive state. To provide insights into possible mechanisms and influence of obesity, 8 lean and 12 obese subjects [106 +/- 11% (SD) and 193 +/- 31% of reference table weight, respectively] eating previously isocaloric diets were exercised to exhaustion (7 +/- 3 min) on a cycle ergometer, then followed for 60 min of recovery. The obese subjects at rest had slightly increased plasma glucose and insulin and elevated blood glycerol concentrations. Both lean and obese subjects had little or no changes in plasma glucose or insulin during exercise, but the increases during the recovery period were greater and/or sustained longer in the obese. Such results raise the possibility of transient hepatic insulin resistance after exercise and are possibly relevant to restoration of depleted muscle glycogen. Both groups had a marked fall in plasma FFA during exercise; the reduction was sustained in the lean but not in the obese subjects. Blood glycerol increased during the recovery period to higher values in the obese than in the lean subjects. Plasma norepinephrine increased about 4-fold in both groups, returning promptly to preexercise values. In contrast, the exercise-induced increment in plasma epinephrine [values at exhaustion, 933 +/- 548 vs. 1970 +/- 787 pmol/L; P less than 0.005] was markedly attenuated in the obese subjects. Thus, the obese subjects had exercise-induced changes in glucose and inulin metabolism consistent with greater postexercise insulin resistance, despite an impaired plasma epinephrine response to intense exercise.
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PMID:Metabolic responses to intense exercise in lean and obese subjects. 264 9

The effects of obesity, weight loss and weight maintenance on the serum lipid levels and lipoprotein lipase and hepatic triglyceride lipase were investigated in rats. Obesity induced by high-fat (HF) feeding was associated with decreased serum triglyceride levels (HF: 70.3 +/- 8.2, control (CON): 140.0 +/- 26.9 mg/dl, P less than 0.05), increased lipoprotein lipase (LPL, HF: 593.2 +/- 10.6 vs CON: 280 +/- 19.5 nmol FFA/min per mg tissue, P less than 0.05) and suppressed hepatic triglyceride lipase activities (HTGL, HF: 14.2 +/- 0.5 vs CON: 18.0 +/- 0.4 nmol FFA/min per mg tissue, P less than 0.01). After a weight loss to the level of control rats, weight maintenance was achieved either by high-protein (HP) or chow feedings (CH). Both high-protein (HFHP) and chow (HFHC) groups had similar weights but only high-protein feeding restored the normal body compositions. Both groups of rats had higher total (TC, HFHP: 146 +/- 10.7; HFCH: 104.8 +/- 5.1 mg/dl), and high density lipoprotein cholesterol levels (HDL-C, HFHP: 100.8 +/- 15.6; HFCH: 75.5 +/- 5.5 mg/dl) and lower lipoprotein lipase (HFHP: 238.2 +/- 15.8, HFCH: 354.8 +/- 34.9 nmol FFA/min per mg tissue) and hepatic triglyceride activities (HFHP: 16.3 +/- 1.1; HFCH: 14.5 +/- 0.6 nmol FFA/min per mg tissue) than control rats (TC: 70.1 +/- 4.7 mg/dl; HDL-C: 14.2 +/- 4.3 mg/dl; LPL: 742.4 +/- 82.3 nmol FFA/min per mg tissue; HTGL: 20.5 +/- 1.0 nmol FFA/min per mg tissue, P less than 0.05 to 0.005) or the rats who regained weight by resuming high-fat feeding (TC: 59.5 +/- 6.7 mg/dl; HDL-C: 10.2 +/- 6.7 mg/dl; LPL: 1284.3 +/- 90 nmol FFA/min per mg tissue; HTGL: 22.2 +/- 1.9 nmol FFA/min per mg tissue, P less than 0.05 to 0.005). The high protein-group had significantly higher total and high-density-lipoprotein cholesterol levels than the chow fed animals despite comparable body weights in both groups. The findings of this study suggest that weight maintenance induced by high protein feeding is more successful in restoring the normal body composition. However, high protein feeding is also associated with high serum cholesterol levels. The clinical applications of these findings need to be evaluated further.
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PMID:Effects of weight loss and weight maintenance on the serum lipids, lipoprotein lipase and hepatic triglyceride lipase activities in obese rats. 276 81

Changes in plasma GH responses to GHRH (1 microgram/kg, iv) were assessed after dietary manipulations in obese and nonobese subjects to determine whether the impaired GH responsiveness to GHRH in obesity is the consequence of obesity per se or of altered food intake. The mean plasma GH response to GHRH in 10 obese subjects was significantly (P less than 0.05) higher after a 72-h fast than when they were eating their usual diet. Comparable increases were found when 6 of the subjects were studied after eating an 800 Cal/day diet for 6 weeks (P less than 0.05). Plasma glucose and insulin levels were lower and FFA levels higher after fasting, but not after the diet, compared to values on the usual diet. The mean plasma somatomedin-C (Sm-C) level was similar to that in nonobese subjects and was unaffected by dietary changes. The peak GH responses to GHRH before fasting were inversely correlated with plasma Sm-C levels (r = 0.64; P less than 0.05). Plasma GH responses to GHRH in normal weight subjects were also higher after fasting for 24 h (P less than 0.05) and 72 h (P less than 0.01) than after an overnight fast. Plasma glucose, insulin, and FFA changes were similar in the obese and normal weight subjects. Plasma Sm-C levels in the nonobese subjects were slightly lower after 72 h of fasting. We conclude that the increased plasma GH responsiveness to GHRH after fasting is not unique to obesity and is unlikely to reflect a reversal of the obesity-associated impairment of GH secretion. The increased plasma GH responsiveness to GHRH after as little as 24 h of fasting suggests that it is a consequence of acute nutrient deprivation rather than weight loss. The enhanced responses in obese subjects after 6 weeks of food restriction, in contrast, are probably a consequence of weight reduction.
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PMID:Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary manipulation in obese and nonobese subjects. 312 15

Recent research has shown the marked differences in association with disease between obesity localized to the abdominal respectively to the gluteal-femoral regions. In this review systematic analyses were performed of the associations between obesity (body mass index, BMI) or abdominal obesity (increased waist-over-hip circumference ratio, WHR) on the one hand, and a number of disease end points, and their risk factors, as well as other factors on the other, WHR was associated with cardiovascular disease, premature death, stroke, non-insulin-dependent diabetes mellitus and female carcinomas. In contrast, BMI tended to be negatively correlated to cardiovascular disease, premature death, and stroke, but positively to diabetes. The established risk factors for these end points were found to correlate to WHR, while this was often not the case with BMI. BMI was positively correlated only to insulin, triglycerides and blood pressure. Together with diabetes mellitus, this seems to constitute a metabolic group of conditions which are thus associated with BMI. Androgens (in women), and perhaps cortisol, seem to be positively, and progesterone negatively correlated to WHR. The WHR was also positively associated with sick leave, several psychological maladjustments, psychosomatic and psychiatric disease. Attempts were made to interpret these findings. In a first alternative an elevation of FFA concentration, produced from abdominal adipose tissue, was considered to be the trigger factor for the pathologic aberrations associated with abdominal distribution of body fat. When obesity is added, the metabolic aberrations may be exaggerated. In a second alternative adrenal cortex hyperactivity was tested as the cause. When combined with the FFA hypothesis, this might explain many but not all of the findings. It seems possible to produce an almost identical syndrome in primates by defined experimental stress. Women with high WHR were found to have a number of symptoms of poor coping to stress. It was therefore suggested that part of the background to this syndrome might be a hypothalamic arousal syndrome developing with stress. It was concluded that obesity and abdominal distribution of adipose tissue constitute two separate entities with different pathogenesis, clinical consequences and probably treatment.
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PMID:The associations between obesity, adipose tissue distribution and disease. 329 56


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