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

In order to study cation transport in vivo the changes in plasma and red cell rubidium concentrations were measured following an oral load of rubidium chloride. Eight patients receiving short-term digoxin therapy, 10 patients with chronic renal failure and 22 patients with untreated essential hypertension were studied, and the findings were compared with those in healthy control subjects matched for age, sex, race, obesity index, and plasma and red cell potassium concentrations. In patients receiving short-term digoxin therapy, and in patients with chronic renal failure, the increases in plasma rubidium concentrations after the oral load of rubidium chloride were significantly enhanced and the increases in red cell rubidium concentrations were significantly attenuated. These findings are consistent with a generalized reduction in Na+, K+-ATPase activity in vivo. In contrast, in patients with untreated essential hypertension the increases in both plasma and red cell rubidium concentrations following the oral load were significantly enhanced. These data do not support the hypothesis that essential hypertension is associated with reduced Na+, K+-ATPase activity in vivo, at least in the red cell.
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PMID:An in vivo study of cation transport in essential hypertension. 610 Jul 48

Concentrations of Na+,K+-ATPase enzyme units are lower in skeletal muscle and liver of adult obese (ob/ob) mice than in their lean counterparts. The present studies were designed to provide information on functional correlates of Na+,K+-ATPase in ob/ob mice. Obese mice had lower potassium (K+) content in muscle and liver and higher sodium (Na+) content in muscle and liver and higher sodium (Na+) content in muscle than lean counterparts. The calculated intracellular Na+/K+ ratio in muscle of obese mice was approximately twice as high as in muscle of lean mice. Oxygen consumption was measured in mice maintained at 14 degrees, 25 degrees, or 33 degrees for 40 min and injected with 0.3 or 0.9 microgram ouabain per g body weight. Ouabain, a specific inhibitor of Na+,K+-ATPase, decreased oxygen consumption less in obese mice (12%--25%) than in lean mice (19%--38%). These results suggest that Na+ pump activity may be reduced in obese mice.
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PMID:Functional correlates of Na+,K+-ATPase in lean and obese (ob/ob) mice. 626 98

1 The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet-induced thermogenesis were studied in rats. 2 A close correlation was found between brown adipose tissue Na+, K+-adenosinetriphosphatase (Na+, K+-ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of noradrenaline on in vitro NA+, K+-ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included beta-adrenoceptor agonists and agents known to induce the release of noradrenaline or inhibit the noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis. 3 Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity. Ciclazindol at doses of 3-30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of mazindol used (0.3 mg/kg i.p.). These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose noradrenaline uptake processes and (b) the relatively high accumulation of ciclazindol in brown adipose. 4 Of the drugs tested, only ciclazindol was a more potent inhibitor of the noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of ciclazindol on the NA uptake system and Na+, K+-ATPase in BAT differed from those of mazindol. 5 These findings suggest that ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human obesity are discussed.
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PMID:Sympathetic mechanisms in diet-induced thermogenesis: modification by ciclazindol and anorectic drugs. 627 18

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

Altered erythrocyte sodium potassium (Na,K)-stimulated adenosine triphosphatase (ATPase) activity has been cited as having pathophysiologic significance in morbidly obese man. Previous studies have failed to consider obese patients after weight loss and, therefore, did not clarify the role of ATPase deficiency as a cause or effect of the obese state. To define more completely the possible alteration of cellular thermogenesis in obesity, a study was made of three groups of people: (1) normal weight controls; (2) morbidly obese; and (3) formerly morbidly obese patients who had lost over 100 pounds after gastric bypass surgery. Erythrocyte ATPase activity was determined by use of an assay that coupled ATPase activity with NADH oxidation in the presence of excess pyruvate kinase, lactic dehydrogenase, and phosphoenolpyruvate. This coupled assay produced a continuous slope so that activity could be calculated from the initial, maximal, linear portion of the decay trace. Results did not demonstrate any statistically significant differences in Na,K-ATPase activity between groups by analysis of variance. A nonsignificant correlation of 0.086 was seen between obesity index and Na,K-ATPase activity. It is concluded that (1) erythrocyte Na,K-ATPase activity is similar in both normal and obese individuals, (2) erythrocyte Na,K-ATPase does not change with weight loss, and (3) therefore, disordered erythrocyte thermogenesis does not have a role in the development or maintenance of obesity.
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PMID:Erythrocyte sodium-potassium-stimulated adenosine triphosphatase activity is not related to obesity. 630 95

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


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