Hormonal regulation of human leptin in vivo:: effects of hydrocortisone and insulin

OBJECTIVE: To investigate the effects of continuous i.v. infusion of hydrocortisone or insulin on leptin secretion in humans. SUBJECTS: Six, nonfasting healthy adults (four women, two men), aged (mean +/- s.e.m.) 36.6 +/- 1.7 y; body mass index (BMI) 27.6 +/- 0.9 kg/m(2). DESIGN: Randomized, placebo-controlled. cross-over study, with a 2-week 'wash-out' period. INTERVENTIONS: Intravenous infusion of hydrocortisone (3.3 mu g/(kg min)), insulin (1 mU/(kg min)) or normal saline (placebo) for 24 h. MEASUREMENTS: Blood sampling every 1-2 h for measurement of glucose, insulin, cortisol and leptin; subcutaneous abdominal fat biopsy for determination of leptin mRNA expression. RESULTS: Plasma cortisol increased to 50.0 +/- 0.4 mu g/dl during hydrocortisone infusion, but was unaltered during saline or insulin infusion. The plasma insulin levels were: 28.5 +/- 4.7 mu U/ml (placebo), 40.8 +/- 9.2 mu U/ml (hydrocortisone, P = 0.214), and 243 +/- 23.0 mu U/ml (insulin, P = 0.0002). Peak hyperleptinemia occurred after 16 h of insulin and 20 h of hydrocortisone infusion; peak/baseline plasma leptin levels (ng/ml) were 18.2 +/- 4.2/15.1 +/- 3.3 (placebo, P = 0.056), 42.1 +/- 7.0/16.0 +/- 3.8 (hydrocortisone, + 163%, P = 0.008) and 30.2 +/- 4.3/16.6 +/- 2.7 (insulin, + 8396, P = 0.024), Adipocyte leptin mRNA increased by 350% after the hydrocortisone infusion. CONCLUSION: Hydrocortisone, a natural glucocorticoid, induces hyperleptinemia in vivo, with a potency greater than that of insulin. The interaction between glucocorticoids and leptin may be of metabolic significance in humans.