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

Plasma cortisol response induced by 2.5 microgram/kg beta 1-24 corticotropin (1 hour infusion) in obese females was not related to fat mass. The response was increasingly pronounced as fat predominated in the upper body segment, i.e. android obesity. This phenomenon may be interpreted as indicating an increased adrenal capacity to secrete cortisol in such obese patients. Low level but longstanding excess cortisol secretion is probably the cause of the android features of obesity.
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PMID:[Plasma cortisol response to intravenous beta 1-24 corticotropin as related to the fat mass and its topographic localisation (author's transl)]. 22 18

All classical adrenoceptor subtypes are functionally expressed in fat cells. However, only beta 1 adrenoceptors appear to be present in all types of fat cells. There is a substantial adrenoceptor reserve in fat cells; approximately 50% of beta and alpha 2 adrenoceptors are spare receptors. Beta adrenoceptors are subject to intensive regulation. They are regulated by insulin, estrogens, and androgens as well as by thyroid hormones and are altered by nutritional factors, diabetes, autonomic neuropathy, and beta-blocking treatment. Alpha receptors are less sensitive to changes except during infancy, when there are marked developmental alterations in the function of alpha 2 adrenoceptors, and during fasting, when there is a decrease in receptor expression. In addition, beta adrenoceptors but not alpha 2 adrenoceptors are sensitive to homologous desensitization after exposure to agonists. Site variations in the expression and function of beta and alpha 2 adrenoceptors, which in part are situated at the level of gene transcription, may be involved in the development of regional obesity.
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PMID:Adrenergic receptor function in fat cells. 130 80

Increasing energy expenditure by treatment with thermogenic drugs is not new, but available drugs have suffered from the problem of lack of selectivity. In the last decade two key findings have allowed the development of selective thermogenic drugs that have promise in the treatment of obesity. 1) The recognition that brown adipose tissue (BAT) plays a role in compensatory increases in energy expenditure has allowed an approach directed at a target organ. 2) The demonstration showing that increases in the activity of BAT may be modulated by an atypical (beta 3) adrenoceptor has led to the development of a new peripherally acting beta-adrenoceptor agonist ICI D7114, which stimulates thermogenesis at doses that have little effect on beta 1 or beta 2 adrenoceptors. Treatment with the compound activates BAT and thermogenesis even in species and situations where the intrinsic capacity is low. 3) The compound has beneficial effects in animal models of obesity and disturbed glucose and lipid homeostasis.
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PMID:ICI D7114: a novel selective adrenoceptor agonist of brown fat and thermogenesis. 134 91

The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (8) has been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 10. Potency was generally markedly reduced by placing substituents on the phenyl ring of the phenoxypropanolamine unit of 8; only the 2-fluoro analogue 16 had comparable potency to 8. Other structure-activity relationships are discussed. Further testing of 8 (ICI 198157) has shown that in the rat it stimulates the beta 3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta 1 and beta 2 adrenergic receptors in other tissues. It increases metabolic rate, as judged by an increase in oxygen consumption, and in the genetically obese Zucker rat it causes a reduced rate of weight gain. This class of compound may be useful in the treatment of obesity in man.
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PMID:Selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis. 1. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetates. 135 Mar 9

The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH). Amides have been examined to determine whether they have advantages over the ester. In particular, in the rat and dog the half-lives of amides of appropriate potency were no longer than those of the ester. The amide (S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2- methoxyethyl)phenoxyacetamide [S-27, ICI D7114] was selected as having properties consistent with a sustained-release formulation should that prove necessary. Unlike the ester it is resistant to hydrolysis in the gut lumen. Further testing of ICI D7114 has shown that in the rat, cat, and dog it stimulates the beta 3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta 1- and beta 2-adrenergic receptors in other tissues. Slimming effects were observed in the dog. ICI D7114 may be a selective thermogenic agent in man and may be useful in the treatment of obesity and diabetes.
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PMID:Selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis. 2. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetamides. 135 Mar 10

With the rapidly increasing average age of the population of the Western world, care and treatment of the elderly are becoming increasingly important. Cardiovascular diseases are major causes of death and disability in the elderly; hence, identification of cardiovascular risk factors and effective treatment are essential. Evidence indicates that these risk factors in the elderly are similar to those in the young; namely, high blood pressure, hyperlipidemia, glucose intolerance, hyperfibrinogenemia, obesity, and cigarette smoking. The latter two relate to general patient management, whereas the remainder can be significantly influenced by modern drug therapy such as celiprolol. This drug is a third-generation highly selective beta 1-adrenoceptor antagonist with beta 2-agonist and vasodilatory activity giving a unique and advantageous pharmacologic profile for antihypertensive therapy with particular benefits for the elderly. The impact of therapy with celiprolol on the cardiovascular risk factors in the elderly hypertensive patient is reviewed.
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PMID:Efficacy of celiprolol in the elderly hypertensive patient. 167 27

The beta 3-adrenoceptor agonist, BRL 26830A, which is not inhibited by either beta 1 or beta 2-selective antagonists, has been shown to possess anti-obesity and anti-diabetic actions. However, the effects of this agent on insulin and glucagon release have not yet been substantiated. Therefore, we tested the hypothesis that BRL 26830A promotes insulin and glucagon secretion via beta 3 receptors on pancreatic islet B and A cells. In ICR mice fasted for 48 h, BRL 26830A significantly stimulated insulin secretion from 5 min after administration, markedly decreased blood glucose levels from 30 min after administration, and significantly increased glucagon secretion from 30 min after administration. The administration of a non-selective beta-receptor antagonist, at a dose of 50 mg/kg, 30 min prior to BRL 26830A injection completely abolished the effects induced by BRL 26830A. However, the administration of a beta 1-selective antagonist at doses of 50 or 100 mg/kg did not produce any significant effects. On the action of BRL 26830A, whereas the administration of a beta 2-selective antagonist at 50 mg/kg, a near maximal effective dose, partially abolished the effects of BRL 26830A. BRL 26830A had no effect on insulin, glucagon, or glucose levels in streptozocin (STZ) diabetic mice fasted for 48 h. These results suggest that, in mice, BRL 26830A may promote insulin secretion mainly via beta 3 receptors and partially via beta 2 receptors on pancreatic-islet B cells, and that glucagon may be secreted as the result of hypoglycemia induced by this agent.
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PMID:Effects of a beta 3-adrenoceptor agonist, BRL 26830A, on insulin and glucagon release in mice. 168 48

Half of the mice in both the monosodium-L-glutamate (MSG)-induced obesity and saline control groups were given BRL 26830A via a gastric tube at a daily dose of 5 mg/kg for 2 weeks, and the other half given distilled water. BRL 26830A administration significantly increased guanosine-5'-diphosphate (GDP)-binding in brown adipose tissue (BAT) and the resting metabolic rate (RMR), and significantly reduced retroperitoneal white adipose tissue (WAT) pads in both groups. It also markedly reduced body weight in MSG obese mice that had reduced BAT thermogenesis and decreased RMR. However, food intake was unchanged in both groups. Neither beta 1- nor beta 2-selective antagonists affected the increase of RMR induced by BRL 26830A, but a non-selective beta-antagonist completely inhibited its increase. These results suggest that BRL 26830A, which is a new beta-adrenoceptor agonist, stimulates BAT thermogenesis, increases RMR, and reduces WAT, thus contributing to the mitigation of obesity.
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PMID:Mitigation of obesity by BRL 26830A, a new beta-adrenoceptor agonist, in MSG obese mice. 197 62

The effects of a combined treatment with supraphysiological doses of the thyroid hormone T3 (15 micrograms/kg BW/day, s.c.) and high doses of a predominant beta 1-blocker (atenolol, 12.5 and 25 mg/kg BW, 3X/day, s.c.) or a non-specific beta-blocker (propranolol, 5 mg/kg BW s.c. and 33 mg/kg BW p.o., each 3X/day) on energy intake, body composition and the heart were studied in overfed rats with an increased body fat content. The goal of the study was to investigate whether the above treatment constitutes a therapy for obesity in that T3 causes weight and fat loss and the beta-blockers prevent the unwanted T3-effects on the heart (tachycardia and increased heart weight). T3 did not increase energy intake above the level seen in overfed animals. It caused loss of body weight due to loss of fat but not protein, an increase in interscapular brown adipose tissue (IBAT) weight and fat, tachycardia and an increase in heart weight. Atenolol and propranolol blocked T3-induced tachycardia. With the exception of the highest propranolol dose which abolished the T3-induced increase in IBAT fat content, the beta-blockers did not modify the other T3 effects. Thus, in spite of the weight and fat loss and the lack of significant protein loss and tachycardia observed under T3/high dose beta-blockers treatment, the T3-induced increase in heart weight makes this treatment unsuitable as a therapy for obesity.
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PMID:T3 plus high doses of beta-blockers: effects on energy intake, body composition, bat and heart in rats. 198 82

The anatomic distribution of fat is related to the risk for obesity-associated morbidity. Among individuals with equal degrees of relative adiposity, those with an upper-body preponderance of fat distribution (android) have higher rates of diabetes, stroke, ischemic heart disease, and early death than those with preferential deposition of adipose tissue in lower portions of the body (hips, thighs, buttocks; gynecoid. There are well-documented anatomic site-related differences in the relative activities of the adrenergic receptors (beta 1----lipolysis; alpha 2----antilipolysis) that control lipolysis. We assessed modifications of the status of alpha 2- and beta 1-adrenergic receptor and subreceptor function in small fragments of adipose tissue obtained by needle biopsy from the gluteal and abdominal subcutaneous regions of five android, seven gynecoid, and six uniformly obese women during a period of weight maintenance (4 weeks) (T1), and after 15% weight loss on an 840 kcal/d diet (T2). Measurements of body shape and adipocyte size were made and related to changes in the metabolism of these adipocytes. The waist-to-hip ratio (WHR) was used to define these three types of regional distribution of fat in these obese subjects: android = WHR greater than 0.86; gynecoid = WHR less than or equal to 0.76; uniform = WHR greater than 0.76 less than or equal to 0.86. WHR was not significantly altered by weight loss in any of the three groups. Although significant effects of time and/or anatomic site on in vitro responses to isoproterenol, norepinephrine, clonidine, forskolin, and dibutyryl cAMP were found, these did not correlate with intra-individual changes in anthropometry or adipocyte size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional changes in adrenergic receptor status during hypocaloric intake do not predict changes in adipocyte size or body shape. 215 70


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