Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots.

Abstract

Regional differences in lipolysis, with higher lipolytic activity in visceral than subcutaneous fat, are important for the development of insulin resistance and might be influenced by testosterone. We studied testosterone-regulated lipolysis and protein expression (by western blot) in fully differentiated pre-adipocytes from visceral (omental) and abdominal subcutaneous adipose tissue from 52 human subjects. These cells were isolated and cultured in a serum-free medium. Testosterone caused a specific, time- and concentration-dependent 50% reduction of catecholamine-stimulated lipolysis in the subcutaneous depot. Half of the maximum effect occurred at 10 nmol/l. The inhibitory effect was due to the inability of beta-adrenoceptors and cyclic AMP to stimulate the protein kinase A, hormone-sensitive lipase complex. Testosterone caused a depot-specific 50% reduction of the protein expression of hormone-sensitive lipase and beta(2)-adrenoceptors in differentiated subcutaneous pre-adipocytes, but no change in beta(1)-adrenoceptors, protein kinase A subunits or perilipin expression. In contrast, testosterone had no effect on lipolysis or protein expression in the visceral depot. However, testosterone receptors were present in both depots, and the hormone inhibited adipocyte leptin secretion. Similar effects on lipolysis were observed with dihydrotestosterone. Testosterone in physiological concentrations causes a depot-specific reduction of catecholamine-stimulated lipolysis in subcutaneous fat cells, probably due to reduced protein expression of beta(2)-adrenoceptors and hormone-sensitive lipase. This could be an important pathogenic factor underlying regional differences in lipolysis and development of insulin resistance and hyperandrogenic polycystic ovary syndrome.