Leptin Response to Glucocorticoid Occurs at Physiological Doses and Is Abolished by Fasting

Abstract

OBJECTIVE: To examine the effects of graded doses of hydrocortisone (HC) on leptin secretion, and determine the effect of fasting. RESEARCH METHODS AND PROCEDURES: This was a randomized, placebo-controlled, crossover study, with a 1-week "washout" period between interventions. Eight healthy subjects [age = 36 +/- 2.3 years (+/-SE), body mass index = 31.5 +/- 1.6 kg/m(2)] completed the dose-response study in which an intravenous infusion of saline (placebo) or HC (30 or 100 mg) was administered for 24 hours. Four healthy subjects (age = 35.2 +/- 3.0 years, body mass index = 27.1 +/- 2.1 kg/m(2)) completed the fasting study, which entailed continuous infusion of saline, HC (300 mg/24 hours) in the fed state, or HC (300 mg/24 hours) with total caloric deprivation for 24 hours. Blood sampling was performed every 1 to 2 hours for measurement of leptin, cortisol, insulin, and glucose levels. RESULTS: Peak hyperleptinemia occurred after 16 hours of HC infusion; peak/baseline leptin levels were 129% (placebo), 140% (30 mg of HC for 24 hours, p = 0.05), and 185% (100 mg of HC for 24 hours, p < 0.01). During infusion of HC (300 mg/24 hours or placebo), the peak/baseline plasma leptin levels were 16.1 +/- 5.8/12.8 +/- 5.9 ng/mL (placebo with food, 126%), 14.6 +/- 6.0/12.5 +/- 6.5 ng/mL (HC fasting, 117%), and 32.5 +/- 12.5/12.0 +/- 8.4 ng/mL (HC with food, 271%, p < 0.001). DISCUSSION: Leptin secretory responses occur at physiological doses of HC, are obliterated by fasting, and thus may be of metabolic significance.