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

Regional variations in adipocyte lipolysis between subcutaneous and visceral fat may be important for obesity complications. In the present study, we compared adrenergic regulation of lipolysis in omental and subcutaneous adipocytes from obese (n = 15) and non-obese (n = 14) male subjects. Waist-to-hip ratio, blood pressure, plasma insulin, and plasma triglycerides were increased in obesity. No regional differences in adrenoceptor lipolytic function were observed in non-obese subjects with the exception of a slight increase in noradrenaline sensitivity in omental adipocytes (P < 0.05), because of increased beta(1)-adrenoceptor sensitivity (P < 0.05). In the obese subjects, the rate of noradrenaline-induced glycerol release was 2-fold higher (P < 0.005) and the noradrenaline sensitivity was 3-fold higher (P < 0.05) in omental versus subcutaneous adipocytes. These findings were mainly due to a 50-fold increase in omental beta(3)-adrenoceptor sensitivity (P < 0.002) and to a smaller 6-fold increase in omental beta(1)-adrenoceptor sensitivity (P < 0.02), accompanied by increased beta(3)- as well as beta(1)-adrenoceptor lipolytic rates at approximately 50% receptor subtype occupancy by the agonist (P < 0.05). In conclusion, minor regional differences in adipocyte lipolytic response to catecholamines are present in non-obese males. In contrast, catecholamine-induced lipolysis is markedly increased in omental as compared to subcutaneous adipocytes in obese males, mainly due to an increase in beta(3)-adrenoceptor function of visceral fat cells, in combination with a smaller increase in beta(1)-adrenoceptor function.
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PMID:Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. 914 94

Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.
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PMID:Modulation of vascular function by diet and exercise. 924 51

1. Sibutramine is a novel 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI) which is currently being developed as a treatment for obesity. Sibutramine has been shown to decrease food intake in the rat. In this study we have used a variety of monoamine receptor antagonists to examine the pharmacological mechanisms underlying sibutramine-induced hypophagia. 2. Individually-housed male Sprague-Dawley rats were maintained on reversed phase lighting with free access to food and water. Drugs were administered at 09 h 00 min and food intake was monitored over the following 8 h dark period. 3. Sibutramine (10 mg kg-1, p.o.) produced a significant decrease in food intake during the 8 h following drug administration. This hypophagic response was fully antagonized by the alpha 1-adrenoceptor antagonist, prazosin (0.3 and 1 mg kg-1, i.p.), and partially antagonized by the beta 1-adrenoceptor antagonist, metoprolol (3 and 10 mg kg-1, i.p.) and the 5-HT receptor antagonists, metergoline (non-selective; 0.3 mg kg-1, i.p.); ritanserin (5-HT2A/2C; 0.1 and 0.5 mg kg-1, i.p.) and SB200646 (5-HT2B/2C; 20 and 40 mg kg-1, p.o.). 4. By contrast, the alpha 2-adrenoceptor antagonist, RX821002 (0.3 and 1 mg kg-1, i.p.) and the beta 2-adrenoceptor antagonist, ICI 118,551 (3 and 10 mg kg-1, i.p.) did not reduce the decrease in food intake induced by sibutramine. 5. These results demonstrate that beta 1-adrenoceptors, 5-HT2A/2C-receptors and particularly alpha 1-adrenoceptors, are involved in the effects of sibutramine on food intake and are consistent with the hypothesis that sibutramine-induced hypophagia is related to its ability to inhibit the reuptake of both noradrenaline and 5-HT, with the subsequent activation of a variety of noradrenaline and 5-HT receptor systems.
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PMID:Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat. 928 94

1. The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. 2. Sibutramine (3 and 10 mg kg-1, p.o.) and (+)-fenfluramine (1 and 3 mg kg-1, p.o.) produced a significant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. 3. Fluoxetine (3, 10 and 30 mg kg-1, p.o.), and nisoxetine (3, 10 and 30 mg kg-1, p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg-1, p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. 4. Venlafaxine (100 and 300 mg kg-1, p.o.) and duloxetine (30 mg kg-1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration. 5. The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of fluoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity.
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PMID:Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat. 928 14

Animal studies have provided clearcut evidence that sympathetic factors are involved in the development and maintenance of high blood pressure (BP). This also appears to be the case in humans, in which sympathetic activation, detected through plasma noradrenaline measurement, noradrenaline spillover technique and direct recording of muscle sympathetic nerve activity, has been shown to characterize the early phases of the hypertensive state and parallel its severity. Sympathetic factors also play in a variety of pathophysiological states frequently associated with hypertension, such as obesity, insulin resistance and atherosclerosis. In addition evidence has been collected that adrenergic factors represent one of the mechanisms involved in determining BP variability, which is strictly associated with end organ damage. Taken together these findings underline the importance that the therapeutical approach to hypertension is aimed not only at lowering BP but also at reducing sympathetic activity.
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PMID:Sympathetic activity, blood pressure variability and end organ damage in hypertension. 932 34

Changes in the activity of the sympathetic activity are often involved in the development of human insulin-resistance syndrome. However, the nature of changes in both the parasympathetic and orthosympathetic components are still controversial. We have recently developed an experimental model reproducing in dog this morbid triptyque (obesity, hypertension and hyperinsulinism), obtained by hypercaloric hyperlipidic diet. The aim of the present study was to characterize the changes in autonomic nervous system and spontaneous baroreflex in the initial period of obesity-hypertension syndrome. Ten male Beagle-Harrier dogs were used in this study. We investigated before and during 20 weeks after the beginning of the hypercaloric diet, plasma insulin, noradrenaline levels, spontaneous baroreflex efficiency (using the sequence method), arterial blood pressure, heart rate and their spectral analysis (fast Fourier Transformation) in both low (LF: 50-150 mHz, reflecting sympathetic activity) and high (HF: respiratory rate +/- 50 mHz, reflecting parasympathetic activity) frequency bands. Body weight (+20%), systolic (SBP: +23%) and diastolic (+16%) blood pressure and heart rate (+19%) increased during 6 weeks and then remained stable. Concomitantly, high frequency of HR (22.01 +/- 1.9 vs 14.15 +/- 1.04% at 7th week) and BF of systolic blood pressure (15.6 +/- 1.1 vs 19.2 +/- 1.2% at 4th week); p < 0.07, showed a rapid decrease in parasympathetic tone and a early increase in sympathetic activity. Nevertheless, in steady state of this syndrome, parasympathetic tone returned to initial values (18.43 +/- 3.25% at 20th week). Insulinemia significantly increased from the 4th week (14.2 +/- 0.9 vs 25.3 +/- 2.2 microUI/mL at 20th week), but noradrenaline remained not modify (400 +/- 85 vs 312 +/- 45 pg/mL at 20th week). Spontaneous baroreflex efficiency also decreased from the 2nd week (35.5 +/- 5.5 vs 16.7 +/- 4.9 mmHg/ms at 20th week). This study shows that an hyperlipidic hypercaloric diet induces a decrease in both parasympathetic tone and spontaneous baroreflex efficiency, which could be the physiopathological link between obesity, hypertension and hyperinsulinism.
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PMID:[Autonomic nervous system abnormalities in the initial phase of insulin resistance syndrome. Value of the study of variability of cardiac rate and blood pressure on a model of nutritional obesity]. 940 26

Sibutramine (SIB), an inhibitor of serotonin and noradrenaline reuptake, has been shown in clinical trials to be associated with a dose-related decrease in bodyweight. This double-blind, placebo-controlled, Latin square crossover study examined whether the effect on bodyweight could be due in part to a reduction in daily food intake. Twelve non-dieting, women with obesity (body mass index of 30.5 to 41.9) received three treatments (0 [matching placebo], 10, or 30 mg SIB/day) for 14 days, with 14-day washout periods in between. On days 7 and 14, participants came to the laboratory to eat breakfast, lunch, and dinner so that daily energy and macronutrient intakes and ratings of hunger and satiety could be measured. Significant reductions occurred in food intake (both grams and energy) over the 14-day study period. On day 7, SIB 30 reduced intake significantly by 1762 kJ (23% reduction from placebo), and on day 14, both SIB 10 and SIB 30 significantly reduced intake compared with placebo (SIB 10, 19% reduction [1490 kJ]; SIB 30, 26% reduction [2079 kJ]). On day 7, the percentage of energy consumed from carbohydrate increased significantly with the 30-mg dose (56.7%) compared with that of placebo (51.4%), with a reciprocal decrease in energy from fat (27.8% to 24%). The results show that SIB reduced energy intake in women with obesity who were not attempting to lose weight.
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PMID:Sibutramine reduces food intake in non-dieting women with obesity. 952 64

The role of brown adipose tissue in total energy balance and cold-induced thermogenesis was studied. Mice expressing mitochondrial uncoupling protein 1 (UCP-1) from the fat-specific aP2 gene promoter (heterozygous and homozygous aP2-Ucp transgenic mice) and their nontransgenic C57BL6/J littermates were used. The transgenic animals are resistant to obesity induced by a high-fat diet, presumably due to ectopic synthesis of UCP-1 in white fat. These animals exhibited atrophy of brown adipose tissue, as indicated by smaller size of brown fat and reduction of its total UCP-1 and DNA contents. Norepinephrine-induced respiration (measured in pentobarbital sodium-anesthetized animals) was decreased proportionally to the dosage of the transgene, and the homozygous (but not heterozygous) transgenic mice exhibited a reduction in their capacity to maintain body temperature in the cold. Our results indicate that the role of brown fat in cold-induced thermogenesis cannot be substituted by increased energy expenditure in other tissues.
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PMID:Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice. 953 Jan 37

The uncoupling protein (UCP) or thermogenin is a 33 kDa inner-membrane mitochondrial protein exclusive to brown adipocytes in mammals that functions as a proton transporter, allowing the dissipation as heat of the proton gradient generated by the respiratory chain and thereby uncoupling oxidative phosphorylation. Thermogenesis (heat production) in brown adipose tissue, which is activated in response to cold exposure or chronic overeating, depends largely on UCP activity. Norepinephrine, released from sympathetic terminals and acting via beta-adrenoceptors and cAMP, is the main positive regulator of both UCP synthesis and activity. Brown fat thermogenesis plays a critical role in thermoregulation and in overall energy balance, at least in rodents. Manipulation of thermogenesis, whether through UCP or through analogous uncoupling proteins, could be an effective strategy against obesity.
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PMID:The uncoupling protein, thermogenin. 959 49

Two putative sympathetic nervous system (SNS) markers, noradrenaline and neuropeptide Y (NPY) were related to 24-h ambulatory blood pressure (BP) in 59 normotensive subjects, 34 non-insulin-dependent diabetics, and 25 controls. Plasma NPY levels were not significantly different between the two groups [non-insulin-dependent (NIDDM) diabetes mellitus 4.33 (3.25-5.78), controls 5.68 (3.39-6.97) p=0.26] as were those of noradrenaline (1.51+/-0.69 versus 1.78+/-0.55; p=0.053). There were correlations, controlled for age and obesity, of plasma NPY with clinic and night time diastolic BP in the control group only (r=0.49 [p=0.013] and r=0.48 [p=0.023] respectively). No similar correlation was found in the NIDDM group, or between plasma noradrenaline and blood pressure in either group. No correlation was found between plasma insulin and NPY or noradrenaline levels. There is a weak independent relationship between NPY and blood pressure in normotensive nondiabetics but not in NIDDM subjects. We found no evidence for the hypothesis that insulin modulates blood pressure through activity of the SNS.
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PMID:Lack of relationship between sympathetic nervous system activity, measured by two circulating markers, and blood pressure in diabetic and nondiabetic subjects. 961 69


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