Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677

OBJECTIVE Growth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK-677, In the present study, the effects of MK-677 treatment on serum levels of lept in, thyroid hormones and testosterone were determined. DESIGN This was a randomized, double-blind, and parallel study. Twenty-four healthy obese males, 19-49 years of age, with body mass index (BMI) > 30 k g/m(2) and a waist:hip ratio > 0.95, were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. RESULTS MK-677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant cha nge was observed at 8 weeks. An increase in serum free 3, 5, 3'-triiodothyr onine (free T3) was not detected until 8 weeks of MK-677 treatment (P<0.05 vs, placebo). Peak serum thyroid stimulating hormone (ISH) concentration af ter MK-677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK-677 treatment, mean peak serum TSH concentration was increased (P<0.05 vs, placebo) althou gh it remained within the normal range, Serum peak values of luteinizing ho rmone (LH) and follicle stimulating hormone (FSH) were similar after MK-677 and placebo administration. MK-677 treatment reduced serum total testoster one (P<0.05 vs, placebo) although total testosterone/sex hormone-binding gl obulin (SHBG) ratio (an index of free testosterone) was not changed, CONCLUSION Treatment with the oral GH secretagogue MK-677 transiently incre ased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK- 677 treatment is able to affect circulating factors of importance for adipo se tissue mass and fuel metabolism.