Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor

Induction of lipolysis in murine white adipocytes by a tumour lipid-mobilis ing factor (LMF) was associated with stimulation of adenylate cyclase in ad ipocyte plasma membrane preparations. Induction of lipolysis was attenuated by the adenylate cyclase inhibitor MDL12330A and the protein kinase A inhi bitor H8, suggesting that cAMP was the intracellular mediator of induction, The effect of LMF on adenylate cyclase was responsive to GTP, with low con centrations (0.1 mu M) causing stimulation and high concentrations (10 mu M ) causing inhibition, suggesting the involvement of both stimulatory (G(s)) and inhibitory (G(i)) guanine nucleotide-binding proteins, At a concentrat ion of 10 mu M, propranolol noncompetitively reduced the induction of lipol ysis by LMF. Thus, lipolysis in white adipose tissue during the process of cancer cachexia is mediated by a tumour factor which stimulates cAMP produc tion, possibly through a beta-adrenergic receptor, (C) 1999 Wiley-Liss, Inc .