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

The effect of genetic selection for backfat accumulation on adipose tissue and muscle lipoprotein lipase (LPL) in fetal and neonatal pigs was investigated. Fetal pigs at 110 d of gestation were taken surgically from sows of either a high backfat (High) or low backfat (Low) line of Yorkshire pigs selected over 18 generations on the basis of backfat thickness at 80 kg live weight. Fetuses of Yorkshire (Control) and Ossabaw (Obese) sows were used for comparison. Activities of LPL/mg cytoplasm protein in subcutaneous adipose tissue were 2.23 +/- .19, 3.98 +/- 1.06, 6.37 +/- .83 and 7.57 +/- .66 nmol FFA released/min and LPL/g tissue was 34.80 +/- 4.06, 58.36 +/- 14.23, 99.55 +/- 15.15 and 159.94 +/- 9.7, for Low, Control, High and Obese 110-d fetuses, respectively. Muscle (semimembranous) LPL/mg protein was 1.06 +/- 1.17 and 1.39 +/- .20 and LPL/g tissue was 50.11 +/- 6.9 and 59.07 +/- 9.12 for High and Low line fetuses, respectively. Fetal body composition was not different for High and Low lines. In 14 d-old suckling pigs, adipose tissue LPL/mg protein had increased to 18.09 +/- 3.48 and 17.76 +/- 3.98 and LPL/g tissue was 291.12 +/- 56.60 and 308.45 +/- 64.43 in High and Low line pigs, respectively. Muscle LPL/mg protein had decreased to .83 +/- .08 in High and 1.25 +/- .13 in Low line pigs, while LPL/g muscle was similar between these lines. These effects of genetic selection on muscle and adipose tissue suggest that early in development, the partitioning of nutrients to lean of fat tissues may be altered, eventually leading to a marked difference in body composition.
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PMID:Muscle and adipose tissue lipoprotein lipase in fetal and neonatal swine as affected by genetic selection for high or low backfat. 717 50

Adipose tissue lipoprotein lipase (ATLPL) is responsible for the provision of lipoprotein-derived fatty acids to adipocytes for storage as triglycerides. Fasting ATLPL has been shown to be decreased in non-insulin-dependent diabetes mellitus (NIDDM), an insulin-resistant state. Medically uncomplicated obesity, another state of relative insulin resistance, is associated with decreased stimulation of the enzyme in response to metabolic stimuli. It was therefore hypothesized that the increased insulin resistance of NIDDM would result in an even greater defect in the response of ATLPL to insulin/glucose. Gluteal adipose tissue biopsies were performed in 13 premenopausal obese women with NIDDM, before and after 6 hours of intravenous insulin and glucose. Metabolic data from these studies were then compared with those obtained from 26 nondiabetic obese women of similar age, weight, and fasting insulin concentration (obese controls [OBC]). As expected, fasting gluteal ATLPL activity was lower in the NIDDM group than in OBC (3.7 +/- 0.9 v 11.1 +/- 1.6 nmol free fatty acids [FFA]/min/10(6) cells, P = .0003). The change in ATLPL activity (delta ATLPL) in response to a 6-hour insulin/glucose infusion was not statistically different between the two groups (2.2 +/- 1.1 v 4.7 +/- 1.2, P = .114). However, in NIDDM subjects there was a strong positive relationship between delta ATLPL and glycohemoglobin (GHb) level (r = .883, P = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycohemoglobin levels relate to the response of adipose tissue lipoprotein lipase to insulin/glucose in obese non-insulin-dependent diabetes mellitus. 747 37

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n = 11, 94 +/- 4 kg, mean +/- SEM) before and after consumption of a 900 kcal day-1 diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n = 11, 82 +/- 4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (3.9 +/- 0.3 nmol FFA min-1 g-1) was similar to that measured in normal weight control women (4.4 +/- 0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs. obese: delta -0.8 +/- 0.3 vs. delta 1.6 +/- 0.5, P = 0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2 +/- 0.3 (obese before weight loss vs. obese after: P = 0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in percent body fat (r s = 0.663, P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase. 765 17

Visceral obesity is strongly associated with insulin resistance. One potential cause is increased availability of FFA. Alternatively, it has been proposed that there is impaired oxidation of lipid in individuals at risk for obesity. The extent to which either concept involves skeletal muscle is uncertain. To examine these opposing hypotheses, 17 healthy lean and obese premenopausal women, among whom cross-sectional area of visceral fat ranged from 18 to 180 cm2, participated in leg balance studies for measurement of FFA and glucose utilization during basal and insulin-stimulated conditions. A metabolic profile of skeletal muscle, based on enzyme activity, was determined in vastus lateralis muscle obtained by percutaneous biopsy. Visceral fat content was negatively correlated with insulin sensitivity (rates of leg glucose uptake and storage), but insulin resistance was not caused by glucose-FFA competition. During hyperinsulinemia, neither leg FFA uptake nor oxidation was increased in women with visceral obesity. During fasting conditions, however, rates of FFA uptake across the leg were negatively correlated with visceral adiposity as were activities of muscle carnitine palmitoyl transferase and citrate synthase. In summary, visceral adiposity is clearly associated with skeletal muscle insulin resistance but this is not due to glucose-FFA substrate competition. Instead, women with visceral obesity have reduced postabsorptive FFA utilization by muscle.
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PMID:Skeletal muscle utilization of free fatty acids in women with visceral obesity. 770 45

Adipocyte plasma membranes were isolated from four patients with type 1a pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gs has been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gs activity, and that this blunted response may lead to decreased lipolysis and to obesity.
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PMID:Defective stimulation of adipocyte adenylate cyclase, blunted lipolysis, and obesity in pseudohypoparathyroidism 1a. 806 43

Changes in body weight, concentrations of urine glucose, blood glucose, plasma insulin and FFA and hepatic enzyme activities were investigated in KK and C57BL mice treated with monosodium-L-aspartate (MSA). MSA was administered subcutaneously to neonates at a dose of 4 mg/g body weight. The MSA-treated KK and C57BL mice were remarkably obese at 10 weeks of age. The average plasma insulin concentration in the control KK mice was 73.6 microU/ml, over 4 times higher than in the control C57BL mice. In the control KK mice, hepatic glucokinase (GK) activity was quite low, and fructose-1,6-bisphosphatase (FBP) and acetyl-CoA carboxylase (CBX) activity was much higher than in the control C57BL mice. In the MSA-treated KK and C57BL mice, the plasma insulin concentration increased to 2 to 3 times higher than in the controls. The MSA-treated C57BL mice showed an increase in GK and CBX activity and acceleration of obesity. In the MSA-treated KK mice, GK activity did not change and CBX activity decreased, and only FBP activity increased significantly. Glycosuria was induced and blood glucose and plasma FFA increased remarkably in all MSA-treated KK mice.
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PMID:Alteration of hepatic enzyme activities in obese KK mice treated with monosodium aspartate. 810 5

Obesity and NIDDM are clearly linked. The subgroup of abdominal, visceral obesity has been shown to have a particularly close link to the development of diabetes. This is probably due to the marked insulin resistance of that condition. Epidemiological data show a predictive power for the development of NIDDM in both sexes, in signs of insulin resistance, visceral obesity and, in women, hyperandrogenicity. In men a relative hypogonadism may be of importance. Experimental evidence suggests cause-effect relationships between these factors. In both sexes visceral fat may contribute to insulin resistance in the liver and the periphery by excess production of FFA. Hyperandrogenicity in women may also cause insulin resistance, although the reverse sequence of events cannot be excluded. The relative hypogonadism may well contribute to insulin resistance in men, as well as to the accumulation of visceral fat. There are observations of additional endocrine aberrations in visceral obesity, suggesting a central, neuroendocrine disturbance, which might be a primary factor for the pathogenesis of the syndrome.
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PMID:Regional obesity and NIDDM. 824 91

The associates of gout-obesity, hypertriglyceridemia, glucose intolerance, and hypertension, strikingly resemble those of insulin resistance. In the present study we determined whether hyperuricemia is associated with insulin resistance and, if so, whether this association can be explained by other components of the syndrome. For this purpose we quantitated insulin sensitivity (euglycemic clamp) in 37 nondiabetic subjects (aged 30-68 yr) exhibiting varying degrees of the metabolic syndrome (body mass index, 21.5-35.7 kg/m2; serum triglycerides, 0.4-22.0 mmol/L; high density lipoprotein cholesterol 0.38-1.86 mmol/L; blood pressure, 190-100/116-60 mm Hg). In simple linear regression analysis, the serum uric acid concentration (range, 182-568 mumol/L) was inversely correlated with insulin sensitivity (rate of glucose utilization; r = -0.61; P < 0.001) and positively with serum triglycerides (r = 0.68; P < 0.001), but not with body mass index, age, or the plasma glucose concentration. In multiple linear regression analysis, both insulin sensitivity (P < 0.05) and serum triglycerides (P < 0.005) were independently associated with the serum uric acid concentration, and together explained 50% of its variation. Addition of body mass index or age to the model did not improve the degree of explanation. Acute elevation of serum triglycerides about 3-fold, of plasma FFA about 9-fold, or of serum insulin about 28-fold had no effect on the serum uric acid concentration in healthy volunteers. The data indicate that hyperuricemia is indeed an inherent component of the metabolic syndrome and could also be used as a simple marker of insulin resistance.
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PMID:Hyperuricemia and insulin resistance. 828 9

An increased supply of FFAs for oxidation leads to a reduced rate of glucose oxidation and interferes with the inhibitory action of insulin on hepatic glucose production. Available evidence indicates that in humans skeletal muscle is a site for such substrate competition, which involves both pyruvate oxidation and glycogen synthesis. The insulin resistance of obesity is thought to be mostly of metabolic origin, and fully reversible. A reduction in FFA supply by weight reduction can, however, reverse this defect. The insulin resistance associated with NIDDM is thought to be primary, with a strong genetic basis, and partially irreversible. Patients with NIDDM are unable to increase their glucose oxidation normally in response to insulin to meet the energy demands of the body. Increased oxidation of lipids represents a compensatory phenomenon to meet these demands. Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has yielded conflicting results. Studies are in progress to develop agents that inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid derivatives seem to enhance glycogen synthesis acutely by activating glycogen synthetase. Whether these or similar agents can be used to restore impaired glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be answered until the effect has been proven in chronic studies. The existence of substrate competition between amino acids and glucose, and an intrinsic hypoaminoacidaemic property of amino acids, makes it possible to expand the Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of substrate disposition at the whole body level.
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PMID:Insulin action and substrate competition. 830 11

To test the hypothesis that the high circulating FFA levels in the diabetes of obesity could contribute to the altered dynamics of insulin secretion seen in that condition, insulin release was measured in isolated perifused rat islet cells, without or with added palmitate. Acutely, as in other systems, palmitate (1 mM) stimulated insulin release. Palmitate (1 mM) suppressed both first and second phase insulin release after 2, 3, or 4 h of perifusion, but not after 1 h. No significant effect was noted with 0.3 mM palmitate, and the effect was maximal at 1 mM. The stimulatory effects of arginine were essentially unaffected. Tolbutamide (1 mM) reversed or counteracted the effect. Glucose oxidation was suppressed in islets incubated with 1 mM palmitate for 4 h. Inhibitors of fat oxidation, alpha-bromostearate (1 mM) and methyl-3-tetradecylglycidate (100 microM) reversed the effects of palmitate on glucose-stimulated insulin release and glucose oxidation. Thus, prolonged incubation of rat islet cells with 1 mM palmitate could suppress the glucose-stimulated release of insulin from perifused rat islets. This suppression could be reversed by inhibitors of fat oxidation. This supports the hypothesis that elevated FFA levels and/or increased fat oxidation could contribute to the altered dynamics of insulin secretion in obese diabetics by fuel antagonism as well as the previously documented suppression of peripheral glucose uptake and stimulation of hepatic gluconeogenesis and may be a key link between obesity and the development of diabetes.
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PMID:Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release. 831 69


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