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

Ingestion of carbohydrate results in a diphasic activation of the sympathoadrenal system. One component is an insulin-mediated activation of the sympathetic nervous system (SNS). This activation is partly a haemodynamic reflex, but it may cause a weak thermogenic effect via beta 1-adrenoceptors in white adipose tissue, the liver and the heart. The second thermogenic component of carbohydrate occurs later when the blood glucose concentration decreases towards baseline levels. This elicits an increased secretion of adrenaline from the adrenal medulla, and the circulating level exceeds the physiological threshold for thermogenic effect. The target is mainly skeletal muscle where thermogenesis is stimulated via beta 2-adrenoceptors. Also the basal metabolic rate and the thermogenic responses to cold and heat exposure, mental stress and exercise, have facultative components. Inhibition of facultative thermogenesis by beta-blockers such as propranolol, diminishes the daily energy expenditure and promotes weight gain and obesity. Although thermogenesis mediated by the sympathoadrenal system accounts for only a small part of the daily energy expenditure, it is sufficient to explain the positive energy balance and weight gain reported in patients receiving treatment with beta-adrenoceptor blocking agents.
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PMID:Effects of nutrient intake on sympathoadrenal activity and thermogenic mechanisms. 225 41

In general, rises in systolic blood pressure to over 200 mm Hg during exercise with a workload of 100W are regarded as pathological. Excessive exercise blood pressure values are to be expected in principle in all hypertensives. However, there are so far no generally accepted criteria for diagnosis of isolated systolic exercise hypertension (with normal values of resting blood pressure). The incidence of isolated systolic exercise hypertension is estimated to be about 10% of a selected population. In patients with excessive rises in blood pressure during exercise who want to engage actively in sport, general measures (reduction of obesity, restriction of alcohol and salt intake) and endurance training should be recommended initially. For endurance training, sporting activities that involve dynamic exercise are to be recommended (walking, running, mountain hiking, cycling, swimming, cross-country skiing). Activities involving isometric exercise (rowing, diving, tennis) and sport of a competitive nature are not suitable. In moderately severe and severe hypertension (diastolic blood pressure values in excess of 105 mm Hg), sporting activities and endurance training are contraindicated. If the exercise blood pressure values cannot be lowered below 220 mm Hg with the general measures mentioned, pharmacotherapy is to be considered. The drugs of choice for suppressing excessive rises in blood pressure during exercise are beta-blockers. In this group, beta 1-blockers are to be preferred to non-selective beta-blockers because of the metabolic neutrality of the former. beta-Blockers without intrinsic sympathomimetic activity (ISA) lower the blood pressure-pulse rate product more effectively than beta-blockers with ISA. Alternatively, calcium antagonists of the verapamil type and ACE inhibitors can be employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of hypertension in actively exercising patients. Implications for drug selection. 264 57

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.
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PMID:Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects. 272 7

The chronic feeding of a sweetened condensed milk/corn oil diet (CM diet) to adult male rats produced significant increases in body weight and levels of plasma insulin in 34% of the rats fed this diet with respect to chow-fed controls. Levels of alpha 1-noradrenergic receptor binding were lower (32%) in the hypothalamic ventromedial nucleus (VMN) of only those rats which became obese (DIO rats) with respect to both chow-fed controls and those rats which resisted the development of obesity on the CM diet (DR rats). Also, alpha 1-noradrenergic binding was inversely proportional to body weight gain in the VMN (r = -0.831). alpha 2-Noradrenergic receptors were 30-37% lower in both the DIO and DR rats in the dorsomedial nucleus and dorsal area of the hypothalamus, and the medial dorsal area and nucleus reuniens of the thalamus. The similar decreases in alpha 2-noradrenergic receptors in both the DIO and DR rats in these areas suggested that dietary factors alone were responsible for these changes. There were no significant differences from chow-fed rats for hypothalamic dopamine (D2) or beta-noradrenergic (beta 1- and beta 2-) receptors in either DR or DIO rats. These results indicate that VMN alpha 1-noradrenergic receptors co-vary with body weight and implicate a role for alpha 1-receptors in the VMN in the central neuronal regulation of body weight.
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PMID:Effects of diet and obesity on brain alpha 1- and alpha 2-noradrenergic receptors in the rat. 284 Oct 11

To investigate the involvement of adrenergic mechanisms in the development of obesity, hyperglycaemia and hyperinsulinaemia in Aston ob/ob mice, the sympathomimetic agent ephedrine (12 mg/kg/day) and the predominantly beta 1-adrenergic antagonist atenolol (12 mg/kg/day) were administered alone and in combination to weanling ob/ob mice for 40 days. Excessive weight gain in ob/ob mice was reduced (15-20%) by ephedrine, exacerbated (8-10%) by atenolol, but not significantly altered by a combination of these agents. The effects of ephedrine and atenolol were lost rapidly (within 5 days) when these agents were withdrawn. Ephedrine slightly reduced the hyperphagia in ob/ob mice, and food intake was transiently increased above that of untreated ob/ob mice when this agent was withdrawn. The development of basal hyperglycaemia and hyperinsulinaemia was not significantly altered by any of the treatments studied. None of the treatments significantly altered body weight, food intake, plasma glucose or plasma insulin concentrations in lean (+/+) mice. The results indicate that a defective adrenergic mechanism involving beta 1-adrenergic receptors contributes to the development of obesity in ob/ob mice.
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PMID:Effects of ephedrine and atenolol on the development of obesity and diabetes in ob/ob mice. 351 92

Studies on BRL 26830A in rodents have shown that thermogenic beta-adrenoceptor agonists have potential for the therapy of obesity. BRL 26830A reduced body weight gain in ob/ob mice and fa/fa rats by reducing lipid accumulation. It had no effect on lean body mass. BRL 26830A did not reduce food intake, its anti-obesity effect being due to stimulation of energy expenditure. This thermic effect was enhanced in the obese animals by repeat dosing. BRL 26830A did not affect body weight gain in the lean counterparts of the obese animals because its thermic effect in lean animals was reduced by repeat dosing. Brown adipose tissue is an important site of BRL 26830A-induced thermogenesis. A single dose of BRL 26830A raised brown adipose tissue temperature, depleted brown adipose tissue lipid and unmasked GDP-binding sites in brown adipose tissue mitochondria. Repeat dosing caused hypertrophy of brown adipose tissue and improved cold tolerance in mice. In-vitro studies showed that the rat brown adipocyte beta-adrenoceptor does not fall into the beta 1/beta 2 classification and BRL 28410, which mediates the biological effects of BRL 26830A in vivo, selectively stimulated the brown adipocyte receptor. It is concluded that BRL 26830A achieves its anti-obesity effect by mimicking natural mechanisms involved in thermogenesis and the control of body weight.
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PMID:Treatment of obesity with thermogenic beta-adrenoceptor agonists: studies on BRL 26830A in rodents. 615 55

Recent studies suggest that thermogenesis in brown adipose tissue has an important role in the regulation of energy balance. Thermogenesis is effected by noradrenaline released from sympathetic nerve endings; the noradrenaline stimulates beta-adrenoceptors, causing lipolysis, and the released fatty acids then promote the uncoupling of oxidative phosphorylation from electron transport. It has been widely accepted that mammalian beta-adrenoceptors exist as two subtypes, beta 1 and beta 2, and rat brown adipocyte beta-adrenoceptors have been classed as beta 1 or as a mixed beta 1/beta 2 population. The beta 1 subtype predominates in atria, whereas the beta 2 subtype predominates in trachea. However, we have now found a novel group of beta-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes. In contrast, isoprenaline, fenoterol and salbutamol are less potent as stimulants of lipolysis than as stimulants of atrial rate or tracheal relaxation. Therefore, beta-adrenoceptors in rat brown adipocytes are of neither the beta 1 nor beta 2 subtypes. Compounds that selectively stimulate brown adipocyte beta-adrenoceptors should have potential as thermogenic anti-obesity agents and this has been demonstrated with BRL 26830A , BRL 33725A and BRL 35135A .
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PMID:Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs. 632 35

beta 3-Adrenergic receptors (beta 3-ARs) are expressed predominantly in white and brown adipose tissue, and beta 3-selective agonists are potential anti-obesity drugs. However, the role of beta 3-ARs in normal physiology is unknown. To address this issue, homologous recombination was used to generate mice that lack beta 3-ARs. This was accomplished by direct injection of a DNA-targeting construct into mouse zygotes. Twenty-three transgenic mice were generated, of which two had targeted disruption of the beta 3-AR gene. Mice that were homozygous for the disrupted allele had undetectable levels of intact beta 3-AR mRNA, as assessed by RNase protection assay and Northern blotting, and lacked functional beta 3-ARs, as demonstrated by complete loss of beta 3-agonist (CL 316,243)-induced stimulation of adenylate cyclase activity and lipolysis. beta 3-AR-deficient mice had modestly increased fat stores (females more than males), indicating that beta 3-ARs play a role in regulating energy balance. Importantly, beta 1 but not beta 2-AR mRNA levels up-regulated in white and brown adipose tissue of beta 3-AR-deficient mice (brown more than white), strongly implying that beta 3-ARs mediate physiologically relevant signaling under normal conditions and that "cross-talk" exists between beta 3-ARs and beta 1-AR gene expression. Finally, acute treatment of normal mice with CL 316,243 increased serum levels of free fatty acids (FFAs) (3.2-fold) and insulin (140-fold), increased energy expenditure (2-fold), and reduced food intake (by 45%). These effects were completely absent in beta 3-AR-deficient mice, proving that the actions of CL are mediated exclusively by beta 3-ARs. beta 3-AR-deficient mice should be useful as a means to a better understanding of the physiology and pharmacology of beta 3-ARs.
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PMID:Targeted disruption of the beta 3-adrenergic receptor gene. 749 88

Beta 3-adrenoceptors is a term used for atypical beta-adrenoceptors which do not fit into either the beta 1- or beta 2-receptor as classified by pharmacological methods. The receptor has been cloned and is thus also genetically defined. Beta 3-adrenoceptors appear to be widely distributed. Until now their importance has been based on studies using agonists with high potency, but yet not selective for beta 3-adrenoceptors. The distribution and functional importance in humans are unclear, and will probably not be clarified before selective antagonists and labelled ligand are developed. Agonists for the beta 3-adrenoceptors may be of clinical value in the treatment of obesity, non-insulin dependent diabetes mellitus, gastrointestinal disorders like irritable colon, inflammatory lung diseases and depression.
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PMID:[Beta 3-receptors: incidence and properties, possible clinical significance]. 784 60

The present study was designed to investigate whether the beta-adrenergically mediated blood flow response of abdominal subcutaneous adipose tissue (per unit adipose tissue weight) was altered in obesity and to study the effect of weight reduction on this response. Body composition (underwater weighing) and fat blood flow were determined in a group of lean (n = 9; % body fat, 11.6 +/- 3.9) and obese (n = 9; % body fat, 28.3 +/- 1.8) subjects. In seven obese subjects, measurements were also performed after a 4-week period of weight reduction induced by a very-low calorie diet (% body fat after diet 23.4 +/- 3.3). After an overnight fast, abdominal subcutaneous fat blood flow was determined by the 133xenon washout technique during a 30-minute period of supine rest and during 30-minute periods of infusion of the beta-agonist isoprenaline (ISO) with and without simultaneous infusion of the beta 1-blocker atenolol (AT). Basal abdominal fat blood flow was significantly higher in lean as compared with obese subjects, whereas weight reduction significantly increased basal fat blood flow (obese v reduced-obese, P < .05). There was a significant increase in abdominal fat blood flow as a result of ISO infusion in lean and obese subjects before and after weight reduction. During ISO+AT infusion, abdominal fat blood flow was still significantly increased as compared with control values in lean and obese subjects. The increase in blood flow during ISO was significantly higher in lean subjects than in obese subjects, whereas the ISO+AT-induced blood flow response was comparable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects. 786 13


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