Regulation of lipolysis in fat cells of obese women during long-term hypocaloric diet

OBJECTIVE: To investigate the influence of four weeks treatment with a strictly defined very low calorie diet (VLCD) on the regulation of adipocyte metabolism in vitro in subcutaneous fat cells of obese subjects. DESIGN: Prospective study. SUBJECTS: Nine obese, but otherwise healthy and drug-free women aged 26-48 years with BMI 36.4-51.9 kg/m(2) were investigated before and during the fourth week on a calorie restricted diet. MEASUREMENTS: A subcutaneous adipose tissue biopsy was obtained from the abdominal area. Isolated fat cells were prepared and incubated in vitro with different agents acting on lipolysis at defined steps in the lipolytic cascade, Glycerol (lipolytic index), hormone-sensitive lipase activity and incorporation of glucose into lipids were measured. RESULTS: VLCD caused a two-fold rise in basal lipolysis (p < 0.005). In spite of this, the maximal lipolytic response of noradrenaline, isoprenaline (non-selective beta-adrenoceptor agonist), dobutamine (beta(1)-adrenoceptor agonist), terbutaline (beta(2)-adrenoceptor agonist), CGP 12177 (beta(3)-adrenoceptor agonist), forskolin (stimulating adenylyl cyclase), dibuturyl cyclic AMP and 8-bromo cyclic AMP (cyclic AMP analogues resistant or sensitive to phosphodiesterase, respectively) were maintained. No differences were found in the hormone-sensitive lipase activity before or during VLCD. The specific alpha(2)-adrenoceptor agonist UK 14304 was equally effective in inducing antilipolysis both before and during calorie restriction. However, during VLCD, the sensitivity and maximal antilipolytic effect of insulin were significantly reduced (p < 0.05) and the ability of insulin to stimulate lipogenesis was almost completely blunted. CONCLUSIONS: Four weeks of VLCD induced elevated basal lipolysis, a resistance to the ability of insulin to induce antilipolysis and lipogenesis in subcutaneous fat cells, but preserved lipolytic catecholamine action, These are factors that together promote fat mobilization and thereby weight reduction during longterm calorie restriction.