Effect of high-fat diet on lypolisis in isolated adipocytes from visceral and subcutaneous WAT.

Variations in total energy intake and composition of daily food play an important role in the regulation of metabolic processes and so, in the control of body weight. This study was designed in order to investigate the effect of a high-fat diet on lipolysis in isolated adipocytes. For this purpose, fourteen Wistar rats were divided into two groups and fed either a standard-fat diet or a high-fat diet ad libitum for 7 weeks. Adipocytes were prepared from fat pads by collagenase digestion and incubated in vitro in the absence or presence of various lipolytic agents. Lipolysis was measured by the release of glycerol into the medium during 90 min of incubation. We observed that a high amount of fat in the diet induced an enlargement of adipose tissue, which was accompanied by a reduction of beta-adrenergic agonist-induced lipolysis, that could be due to a loss of beta(1) and beta(3)-adrenoceptor number or to alterations of their coupling to adenylate-cyclase through the guanine nucleotide regulatory protein. New data about regional differences were provided by comparing two adipose locations (subcutaneous and visceral).

Desensitization effect of in vivo treatment with metaproterenol on beta1, beta2 and beta3-adrenergic responsiveness in rat adipocytes.

The desensitization process of beta-adrenergic system was assessed by in vivo administration to 7-week old rats of a mixed beta-agonist, metaproterenol (3,5-dehydroxyphenyl-N-isopropyl-amine-beta-ethanol sulphate; T1/2=6 hours), (2 mg/kg/d) in treatments of 12 hours, 2 days and 10 days. The in vitro lipolytic effect of selective beta-adrenergic agonists, dobutamine, salbutamol and BRL 37344, as well as plasma free fatty acid concentrations were measured in treated and control animals given vehicle. Different times of exposure to a beta-agonist induced a loss of responsiveness on lipolytic response mediated by beta1 and beta2-adrenoceptors, as demonstrated by decreased affinity and intrinsic activity (maximal effect) of dobutamine and salbutamol. In contrast, no changes were found in beta3 mediated lipolysis. These observations suggest that beta1, beta2 and beta3-adrenoceptors follow different regulatory patterns. Lack of beta3-adrenoceptor desensitization may have important physiological and therapeutic consequences in the treatment of diseases such as obesity and heart failure.

Lipolytic effects of beta1, beta2 and beta3-adrenergic agonists in isolated human fat cells from omental and retroperitoneal adipose tissues.

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.

Effects of the beta-adrenergic agonist salbutamol and its withdrawal on protein metabolism of lambs.

Rasa Aragonesa lambs were used to evaluate the repartitioning effects of a beta-adrenergic agonist and its withdrawal on nutrient metabolism. One group of animals (T-I) was fed salbutamol at a dose of 2 mg x kg-1 diet x day-1 for 38 days, while in another group (T-II) the beta-adrenergic agonist was discontinued in the diet 5 days before slaughter on the 43rd day. The semitendinosus muscle protein content increased (p < 0.05), while fat and collagen content decreased (p < 0.05) in the T-I group. These differences were not apparent in the group from which salbutamol was withdrawn. Muscle protein degradation was diminished (p < 0.05) in both treated groups. The serum free fatty acid level was markedly enhanced (p < 0.05) in the T-I group. Total essential amino acid serum levels were reduced (p < 0.05) after the withdrawal period. Ketogenic and urea cycle amino acids were reduced (p < 0.05) in the salbutamol-fed T-I group and glycogenic amino acids were diminished (p < 0.05) in the T-II experimental group. The data show that salbutamol is able to increase muscle content at the expense of fat stores in productive animals. However, these repartitioning effects are circumvented by a 5-day period of withdrawal, in which concomitant metabolic changes in lipid and protein turnover and plasma amino acid profiles occur.

Organ weights, muscle composition and fatty acid profiles in lambs fed salbutamol: Effect of a 5-day withdrawal period.

Lambs were fed ad libitum on a diet containing the ß-adrenergic agonist salbutamol (2 ppm) for 38 days to investigate its effects on organ weights, muscle composition and fatty acid profiles. The influence of a 5-day withdrawal period was also assessed. The oral administration of salbutamol did not increase muscle weights and no differences were found in liver, heart and lung proportions. However, kidney weight was higher in the salbutamol-not-withdrawn animals. In treated animals fat and collagen levels decreased (P < 0.05), while protein increased (P < 0.05) in the semitendinosus (ST) muscle when compared to controls. However, no effects of the ß-agonist treatment were found in the longissimus dorsi (LD) muscle. Intramuscular LD polyunsaturated fatty acids were higher (P < 0.05). Subcutaneous adipose tissue samples were higher (P < 0.05) in total unsaturated fatty acids and lower (P < 0.05) in total saturated fatty acids. All these changes in the fatty acid profiles of both intramuscular and adipose tissues were more marked after the 5-day salbutamol withdrawal period.