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

Na+, K+ -ATPase activity was measured in red blood cells from 20 nondiabetic euthyroid male Pima Indians with varying degrees of obesity; their body mass indices ranged from 22-60 kg/m2. The na+, K+ -ATPase, measured both by 86Rb uptake in intact cells and ATP hydrolysis by purified membranes, was inversely correlated with body mass index (r = -0.62; P less than 0.005 and r = -0.75; P less than 0.0001, respectively). These results confirm that obesity is associated with decreased Na+, K+ -ATPase in intact red blood cells, and provide the first demonstration of a reduced sodium pump in isolated red cell membrane preparations from obese men.
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PMID:Reduced Na+, K+ -ATPase activity in intact red cells and isolated membranes from obese man. 627 81

Obese (ob/ob) mice have a lower thermogenic capacity than lean mice. The possible role of brown adipose tissue (BAT) in this defect was investigated. Lean and obese mice were exposed to 33 (thermoneutral), 25, or 14 degrees C for up to 3 wk. BAT cytochrome oxidase activity and numbers of Na+-K+-ATPase enzyme units, enzymes involved in thermogenesis, were similar at 33 or 25 degrees C. Chronic exposure to 14 degrees C increased these enzymes 34 and 62%, respectively, in lean mice and nearly 150% in obese mice. Sympathetic nervous system activity, which stimulates thermogenesis in BAT, was evaluated by measuring norepinephrine (NE) turnover. At 25 degrees C, NE turnover rate in BAT of obese mice was only 40% as rapid as in BAT of lean mice. Chronic exposure to 33 degrees C depressed NE turnover in BAT of lean mice, but not in obese mice, whereas exposure to 14 degrees C accelerated NE turnover in both lean and obese mice. Lower sympathetic nervous system activity in BAT of obese mice at 25 degrees C is likely a major factor in their reduced nonshivering thermogenesis and resultant high efficiency of energy storage.
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PMID:Reduced norepinephrine turnover in brown adipose tissue of ob/ob mice. 627 59

Ouabain binding and electrolyte concentrations of erythrocytes, and Na+, K+-ATPase activity of red cell ghosts were measured in normal and obese subjects, ranging from 88-257% of their ideal body weight. All three independent measurements were virtually the same in obese and nonobese groups, and no correlations were found between these three variables and the percentage of ideal body weight. These results differ from previous reports of either increased or decreased sodium pump function and suggest that Na+, K+-ATPase does not directly influence human obesity.
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PMID:Is the erythrocyte sodium pump altered in human obesity? 630 Jan 77

Na, K-ATPase activity may have a significant role in cellular thermogenesis. Reduced thermogenesis and an increased accumulation of unused calories in the form of fat could result from reduced basal or insulin-stimulated Na,K-ATPase activity in obese insulin-resistant man. We have previously demonstrated reduced Na,K-ATPase activity in intact red cells and their isolated membranes from obese humans. To determine if the reduced enzyme activity in obese subjects is the result of inherent cellular defects in the regulation of Na,K-pump activity, basal and insulin-stimulated rates of ouabain-inhibitable Rb uptake were measured in diploid fibroblasts from subjects with a range of body mass indices (BMI). Cell cultures were established from five extremely obese subjects (BMI greater than 40 kg/m2) with fasting hyperinsulinemia (38 +/- 6 microU/mL) and in four control (BMI less than 30 kg/m2) normoinsulinemic (14 +/- 3 microU/mL) subjects. Basal (17 +/- 3 v 23 +/- 2 nmol/L/min/10(10) cells +/- SEM) and maximal insulin-stimulated Na,K-pump activities (26 +/- 3 v 32 +/- 3 nmol/L/min/10(10) cells) were similar in the obese and control subjects. Maximal insulin stimulation for both groups was observed in four to eight minutes, and one-half maximal response required 2.5 ng/ml insulin. Cell density was negatively correlated with basal (r = 0.75, p less than 0.001) and maximally stimulated Na,K-pump activity (r = -0.73, p less than 0.001). Adjustment for this relationship did not influence the conclusions. Comparison of the results from the obese and control groups indicates (a) no evidence for an intrinsic cellular difference in basal Na,K-pump activity related to obesity and (b) no difference in insulin regulation of Na,K-pump activity, in fibroblasts from obese subjects.
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PMID:Sodium-potassium pump in cultured fibroblasts from obese donors; no evidence for an inherent decrease of basal or insulin-stimulated activity. 632 14

The effect of diet-induced obesity on tissue Na, K-ATPase activity ("sodium pump") has been determined in the intact rat exposed to a cafeteria diet. Mature female Charles River rats showed significant increases in carcass lipid on this regimen (P less than 0.01), whereas male rats exposed to cafeteria diet and control male and female animals on laboratory chow showed no increase in carcass lipid over the 54 to 103 days that the animals were studied. In the female cafeteria-diet group, red blood cell membrane Na, K-ATPase activity and carcass lipid were highly correlated (r = 0.847, P less than 0.001). Significant trends in Na, K-ATPase activity as a function of carcass lipid did not occur in either kidney or liver crude membrane preparations from cafeteria-diet females. No correlation was seen in red cell, liver, or kidney membrane Na, K-ATPase with carcass lipid in male cafeteria-diet animals or in the control males and females. In this animal model of nongenetic obesity, changes in tissue Na, K-ATPase activity can be induced by dietary manipulation and are sex-specific and organ-specific.
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PMID:Changes in cell membrane Na,K-ATPase activity associated with induction of dietary obesity in the rat. 633 Apr 93

An insulin-sensitive subcellular system was developed from rat adipocytes consisting of plasma membranes and mitochondria. Direct addition of insulin, concanavalin A or anti-insulin receptor antibody to this system resulted in the production of a mediator substance from the plasma membrane that caused dephosphorylation of the alpha subunit of pyruvate dehydrogenase in the mitochondria with concomitant activation of the enzyme. The mediator activated pyruvate dehydrogenase by activating the pyruvate dehydrogenase phosphatase and not by inhibiting the pyruvate dehydrogenase kinase. This was similar to the mechanism by which insulin causes activation of the enzyme in the intact cell. The insulin-sensitive mediator material from the adipocyte plasma membrane was acid-stable with a molecular weight of 1,000 to 1,500. Our laboratory has shown that the mediator that activates pyruvate dehydrogenase was present in intact adipocytes, hepatoma cells, and IM-9 lymphocytes. Insulin altered the amount or activity of the mediator consistent with the effect of the hormone on the cell. Other laboratories have shown similar effects on skeletal muscle and liver. We have shown the mediator to mimic insulin action on the low Km cyclic adenosine monophosphate (AMP) phosphodiesterase and the (calcium++-magnesium++)-adenosine triphosphatase (Ca++-Mg++)-ATPase of adipocyte plasma membranes in addition to pyruvate dehydrogenase. Other laboratories have shown the mediator to activate glycogen synthase. A body of direct and indirect evidence exists that demonstrates that more than one mediator exists. The chemical nature of the mediator is unknown but probably represents a new family of intracellular mediators of hormone action. These mediators may have clinical relevance in postreceptor defects of obesity and type II diabetes (noninsulin-dependent diabetes mellitus).
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PMID:The chemical mediators of insulin action: possible targets for postreceptor defects. 633 85

The relationship between bodyweight and arterial pressure was first discovered early this century. More recently, epidemiological studies have confirmed the correlation between bodyweight and blood pressure in both adults and children. Serum cholesterol levels, blood glucose levels, uric acid levels and blood pressure increase with increasing bodyweight. In the presence of androgens, upper body obesity, caused by excessive intake of calories, increases cardiovascular risk factors, probably as a result of hyperinsulinaemia. The activity of Na+/K(+)-ATPase in the cells of obese subjects is reduced in a way that may be genetically determined, or may be mediated by changes in plasma insulin levels or a natural inhibitor of Na+/K(+)-ATPase. In vitro studies have shown that the potency of a non-ouabain inhibitor of Na+/K(+)-ATPase is enhanced by the presence of insulin. This may result in vascular smooth muscle having increased reactivity to pressor agents. A knowledge of cellular membrane transport may lead to a better understanding of the epidemiology of obesity-related hypertension.
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PMID:Epidemiology of high blood pressure and obesity. 751 70

Intracellular Ca2+ homeostasis is impaired in tissues from obese humans and rats and insulin loses its regulatory effect on the plasma membrane (Ca2+ + Mg2+)-ATPase in kidney basolateral membranes (BLM) from the genetically obese fa/fa rats. We have demonstrated that loss of insulin regulation of the ATPase may impair insulin biologic effects and may therefore contribute to the insulin resistance in the obese rodents. To test whether the defect is restricted to one species or to one gene of obesity, studies were extended to an additional genetically obese rodent of another species the C57BL/6J ob/ob mice. Twelve-weeks-old obese and control male mice were used and (Ca2+ + Mg2+)-ATPase activity and its regulation by insulin were evaluated in their kidney BLM. The obese mice were heavier (56.4 +/- 2.5 vs 30.5 +/- 1.2 g P < 0.05), were hyperinsulinemic (6.32 +/- 1.87 vs 0.59 +/- 0.13 ng/ml P < 0.05) and had decreased (by 80%) specific binding of insulin to their epididymal fat cells compared with their non-obese littermates controls (ob/+, +/+). Yet, non-fasting plasma glucose levels were similar in the obese and control mice (227.0 +/- 19.3 vs 226.8 +/- 13.7 mg/dl N.S.). Basal activity of the (Ca2+ + Mg2+)-ATPase was similar in membranes from the ob/ob and control mice. However, while insulin (1-40 ng/ml) stimulated the ATPase activity in BLM form controls in a dose dependent manner (15-52%), no effect of insulin on the enzyme was seen in BLM from the obese mice even in the presence of the highest (40 ng/ml) concentration of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different genes for obesity are associated with insulin loss of regulation of the membrane (Ca2+ + Mg2+)-ATPase in the obesity syndrome. Lessons from animal models. 773 47

Hypertension in obesity and insulin resistance has been attributed to insulin stimulation of sympathetic neural output and renal sodium retention. However, recent data demonstrates a significant vasodilatory effect of insulin and suggests that vascular smooth muscle resistance to this action may instead be the cause of hypertension in insulin resistance. This concept is supported by the observation that pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. Insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle relaxation, while these effects are blunted in obesity and insulin resistance. Insulin regulation of vasoconstriction and vascular relaxation appears to be secondary to regulation of intracellular Ca2+ ([Ca2+]i), as insulin attenuates both voltage- and receptor-mediated Ca2+ influx and stimulates both the transcription and activity of Ca(2+)-ATPase in vascular smooth muscle cells. Further, these effects are also blunted in insulin resistance. Although [Ca2+]i plays a poorly understood role in insulin signalling, increases beyond an optimal range results in impaired insulin sensitivity, possibly by Ca(2+)-inhibition of insulin-induced dephosphorylation of insulin-sensitive substrates. Consistent with this concept, ectopic overexpression of the agouti gene in the viable yellow (Avy) mouse results in increased skeletal myocyte [Ca2+]i. Accordingly, increased [Ca2+]i in primary insulin target tissues appears to result in peripheral insulin resistance which then results in aberrant regulation of vascular smooth muscle [Ca2+]i and increases in arterial pressure.
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PMID:Insulin resistance vs. hyperinsulinemia in hypertension: insulin regulation of Ca2+ transport and Ca(2+)-regulation of insulin sensitivity. 778 37

We have previously shown that insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle cell (VSMC) Ca(2+)-ATPase mediated Ca2+ efflux and vascular relaxation. We have now sought to determine if VSMC from insulin resistant (Zucker Obese, ZO) rats manifest exaggerated [Ca2+]i responses to pressor agonists and impaired [Ca2+]i recovery (rate of [Ca2+]i return to baseline) compared to their lean controls (ZL). Thoracic aortae from ZO and ZL were enzymatically digested to release VSMC (n = 16 animals/group and 8 determinations/group). Freshly dispersed cells were washed, counted, and loaded with Fura-2-AM. The [Ca2+]i responses to and rate of recovery from angiotensin II (AII; 200 nmol/L) and arginine vasopressin (AVP; 10 mumol/L) were studied fluorometrically in stirred suspension (10(6) cells/mL). Peak [Ca2+]i responses to AVP were not significantly different in ZO v ZL, while responses to AII were higher in ZL ([Ca2+]i, 180 +/- 7 v 160 +/- 4% of baseline in ZL and ZO, P < .02). Since we have recently shown insulin to increase AII-releasable Ca2+ stores in sarcoplasmic reticulum, this increase in peak [Ca2+]i response to AII in ZL may reflect relative VSMC insulin resistance in ZO. Despite their increased peak AII response, ZL exhibited a more rapid recovery from both the AII-stimulated load (recovery rate, 66.1 +/- 8.9 v 42.1 +/- 9.0 nmol/L/min in ZL and ZO, P < .02) and the AVP-stimulated [Ca2+]i load (22.2 +/- 2.3 v 18.4 +/- 4.6 nmol/L/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats. 834 33


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