Alpha-2 Adrenergic Antilipolytic Effect in Dog Fat Cells: Incidence of Obesity and Adipose Tissue Localization
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Abstract:
The main intention of this study was to characterize the alpha-adrenoceptor responsible for the inhibition of lipolysis in dog fat cell and to define circumstances that may be associated to a modification of the alpha-mediated antilipolytic effect. Isolated fat cells from omental and subcutaneous adipose tissue from normal and obese dogs were used. Basal and theophylline stimulated lipolysis was studied in the presence of selected alpha-adrenergic agonists and antagonists. The antilipolytic effect of catecholamines is mediated by alpha 2-type adrenoceptors in dog fat cell. The alpha-adrenergic responsiveness is enhanced (or unmasked) in large fat cells of obese dogs and depends on the site from which the adipose tissue sample is taken. The alpha-response is stronger in subcutaneous than in omental adipocytes. In conclusion, the weakened lipolytic responsiveness to epinephrine of obese dog fat cells seems related to an increased alpha-adrenergic response rather than a decreased beta-lipolytic effect. Obesity is a circumstance characterized in the dog fat cell by a modification of the balance between alpha-2 and beta receptors.Keywords:
Alpha (finance)
Alpha-2 adrenergic receptor
Basal (medicine)
The presence of beta1- and beta2-adrenoceptors has been clearly established in human fat cells. There is some controversy about the presence and function of beta3-adrenoceptors. It is well established that there are marked regional variations in catecholamine-induced lipolysis. In this work the possibility that a beta3-adrenoceptor plays a significant role in the control of lipid mobilization is studied and also its importance in comparison to beta1- and beta2-adrenoceptors in isolated human fat cells, is evaluated, by measuring the in vitro lipolysis induced by dobutamine, salbutamol, metaproterenol, BRL 37344 and CGP 12177A. Human adipocytes from omental and retroperitoneal fat deposits exhibited an "atypical" beta-adrenergic response but, given the small lipolytic effect initiated by BRL 37344 and CGP 12177A, they are probably poorly equipped in functional beta3-adrenoceptors.
B2 receptor
Fat pad
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Pharmacological properties of adrenergic receptors have been investigated in fat cells isolated from omental adipose tissue of the Dog. From the results, the following points can be stated. 1. Lipolysis is markedly enhanced by isoproterenol. This effect is competitively inhibited by propranolol (a beta-adrenoceptor blocking agent). (Fig 1). 2. The beta 2-sympathomimetic salbutamol is found to have only a slight effect on lipolysis rate (Fig. 2). 3. The epinephrine-induced lipolysis is potentiated by phentolamine (an alpha-adrenoceptor blocking agent) only on large sized adipose cells (mean fat cell size 96.7 +/- 5.3 micrometer; Fig. 5). 4. The isoproterenol-induced lipolysis is partially inhibited by phenylephrine (an alpha-adrenomimetic drug) (Table I). These findings show that beta 1 nature of the receptors involved in the adrenergic control of lipolysis in Dog adipose tissue. Moreover an antilipolytic effect of epinephrine, via alpha-adrenergic receptors, is observed, especially in large adipose cells.
Phentolamine
Phenylephrine
Alpha (finance)
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Abstract Lipolytic activity was studied in brown and white adipose tissue of rats in vitro. 5-Hydroxytryptamine (5-HT), phenylephrine, noradrenaline, adrenaline and isoprenaline were used as adipokinetic agents. All stimulated lipolysis in brown adipose tissue, but 5-HT and phenylephrine did not in white adipose tissue. A β-blocking drug, propranolol, inhibited the stimulatory effect of the agents in both adipose tissues. However, an α-blocking drug, phentolamine, further increased the lipolysis induced by noradrenaline or adrenaline in brown adipose tissue and inhibited the effect of isoprenaline. In white adipose tissue, its action was to marginally decrease the effect of adrenaline and noradrenaline. Increase in the pH of the incubation medium stimulated FFA and glycerol release in brown adipose tissue, but not in the epididymal adipose tissue. This effect of pH on lipolysis was further enhanced by phentolamine and decreased by propranolol. Increase of lipolysis with pH was not seen with brown fat tissue from the reserpine-treated rats. These results show that brown adipose tissue of the rat has an α-receptor with inhibitory effects on lipolysis that is affected by α- or mixed-type adrenergic agonists, noradrenaline and adrenaline.
Phentolamine
Isoprenaline
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Abstract. The regulation of lipolysis has been studied in subcutaneous adipose tissue removed under local anesthesia from hypothyroid patients. As control subjects were used hypothyroid subjects on replacement therapy. Noradrenaline induced no significant increase in lipolysis in tissue removed from hypothyroid patients, while the increase in glycerol release from adipose tissue of the control group was almost twofold. The addition of the alpha‐adrenergic blocking agent phentholamine to noradrenaline‐containing media produced a significant increase in the glycerol release from tissue of the hypothyroid patients as well as from the control subjects. Iso‐propylnoradrenaline, a nearly selective beta‐adrenergic agonist, theophylline or dibutyryl‐cyclic AMP stimulated lipolysis in tissue from both groups. These results indicate that the lipase system cannot be the rate‐limiting factor for the lipolytic response to noradrenaline in adipose tissue from hypothyroid patients. The decreased lipolytic response to noradrenaline in this tissue seems to be due to a more pronounced alpha‐adrenergic effect of noradrenaline counteracting the lipolytic effect mediated by the beta‐adrenergic receptor.
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Abstract. The effects on lipolysis of l ‐noradrenaline, l ‐isopropylnoradrenaline, theophylline and N 6 ‐2′0‐dibutyryl‐adenosine 3,5 monophosphate have been studied on sections of human subcutaneous and omental adipose tissue obtained from 17 subjects undergoing abdominal surgery. In both tissues isopropylnoradrenaline, an almost pure beta adrenergic stimulator, induced higher glycerol release than noradrenaline. The alpha adrenergic blocking agent phentolamine increased the noradrenaline‐stimulated glycerol release in both tissues. These data indicate that catecholamine‐induced lipolysis is mediated by beta adrenergic receptors and is inhibited by alpha receptors. Lipolysis induced by either noradrenaline or isopropylnoradrenaline was greater in omental than in subcutaneous adipose tissue. On the other hand theophylline, which is supposed to increase the tissue level of cyclic AMP, and administration of cyclic AMP itself (the dibutyryl form), induced almost equal lipolysis in both tissues. It is therefore suggested that the lower lipolytic response to catecholamines of subcutaneous adipose tissue is due to a lower formation of cyclic AMP.
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Subcutaneous adipose tissue
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Abstract Aim: To induce lipolysis, catecholamines could reach the adipocyte via the blood stream after being released from the adrenal medulla or, alternatively, via neuronal release in the vicinity of the fat cell. Sympatho‐neuronal effects on fat tissue lipolysis have been demonstrated in experimental animal models. However, the role of sympathetic nerves in the control of lipolysis in human white adipose tissue, which is sparsely innervated, has not been clarified. Conclusion: The present review summarizes evidence for a direct neuronal influence on lipolysis in humans.
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Sympathetic nervous system
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With the help of subcutaneous adipose tissue performed on 0,1- to 10-, 20- to 40- and 60- to 75-year-old test persons the effect of isoprenalin, adrenalin and noradrenalin on the release of glycerol or the unesterified fatty acids was investigated. Independent on age the quantity of the isoprenalin-stimulated lipolysis increases with the size of the fatty acids of the incubated tissues. The specimens of adipose tissue used do not show any differences in the size of the adipocytes between the individual age groups. Amaximum release of glycerol is achieved in a concentration of the medium of 10(-5) mol/l (isopernalin) to 10(-4) mol/l (adrenalin). Isopernalin effects an altogether larger increase of lipolysis in the adipose tissue of the human being of old age in already smaller concentrations compared with other age groups. These findings refer to a higher affinity of adrenergic beta-receptors of the adipocytes in this age period, but also to possible age differences in the chain of lipolysis mediated by cAMP.
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