Sabado

Hormonal control of regional fat distribution
Per Bjorntorp
Department of Heart and Lung Diseases, Sahlgren's Hospital, University of Goteborg, S-413 45 Goteborg, Sweden

Hormones exert powerful influences on body fat distribution in humans. Studies under fully controlled conditions in vitro have indicated that cortisol and insulin facilitate lipid accumulation by expressing lipoproteinlipase (LPL). Growth hormone (GH) abolishes this and turns metabolism towards lipid mobilization. Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Cortisol effects are mediated via a glucocorticoid receptor, and testosterone effects via an androgen receptor, the density of which appears to be higher in visceral than subcutaneous adipose tissue. The receptor-mediated effects areprobably expressed via transcription of appropriate genes. The female sex steroids also regulate adipose tissue metabolism, but apparently not directly in the absence of specific cellular receptors. Oestrogens seem to exert net effects similar to those of testosterone. These results of cellular studies agree well with invivo studies of triglyceride uptake and turnover in different adipose tissue regions.Furthermore, clinical entities with characteristic disturbances in hormone levels show the expected redistribution patterns. Key words: cortisol/growth hormone/human adipose tissue/oestrogen/testosterone

Introduction The regional fat distribution in humans is clearly regulated by hormones, although genetic factors also play important roles. Vague (1947) realized this aspect of fat distribution50 years ago and described the difference between adipose tissue
Human Reproduction Volume 12 Supplement 1 1997

distribution in men and women. Not only sex steroid hormones are of importance, since adrenal corticosteroids also play a major role. This is seen clinically for example in Cushing's syndrome. In addition, peptide hormones such as insulin and growth hormone (GH) are importantregulators of adipose tissue distribution, often on the basis of 'permissive' effects of the steroid hormones. In other words, steroid hormones provide a more long-term adaptation to permit the acute effects of peptide and catecholaminergic hormones. In the following text, the effects of steroid hormones will be reviewed primarily. Furthermore, since adipose tissue metabolism is highly variable amongspecies, human data will be assessed where possible, and animal research will be included only when human data are missing. First, the general effects of hormones on adipose tissue metabolism will be summarized, and then the regional specificity of endocrine action. This area has been reviewed repeatedly recently, and the reader is referred to these works for detailed references (Bjorntorp, 1991,1993). Here a condensed updated version of these reviews is given. In human adipose tissue the regulation of lipid accumulation at the level of the adipocyte is achieved mainly through the activity of lipoprotein lipase (LPL). The de-novo fatty acid synthesis from carbohydrate substrates is of considerably less quantitative importance. Lipid mobilization is regulated by the activity of thehormone-sensitive lipase, which is under the main, 'acute' control of catecholamines (stimulatory) and insulin (inhibitory) in human adipose tissue. There is also a possibility that under certain conditions an incomplete re-esterification of triglycerides may 21

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© European Society for Human Reproduction & EmbryologyP.Bjorntorp

contribute to the mobilization of fatty acids, but information on this process is scarce, probably due to methodological difficulties. Cellular studies Cortisol Cortisol exerts major effects on adipose tissue metabolism, both on lipid accumulation and mobilization. In the presence of insulin, lipoprotein lipase (LPL) is markedly expressed. This expression is regulated by an...