Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues

Growth hormone secretagogues (GHSs) stimulate growth hormone (GH) secretion , which is lipolytic. Here we compared the effects of twice daily s.c. trea tment of GH and the GHS, ipamorelin, on body fat in GH-deficient (lit/lit) and in GH-intact (+/lit and +/+) mice. In +/lit and lit/lit mice ipamorelin induced a small (15%) increase in body weight by 2 weeks, that was not fur ther augmented by 9 weeks. GH treatment markedly enhanced body weight in bo th groups. Ipamorelin also increased fat pad weights relative to body weigh t in both lit/lit and +/lit mice. Two weeks GHS treatment (ipamorelin or GH RP-6) also increased relative body fat, quantified by in vivo dual energy X -ray absorpiometry (DEXA) in GH-intact mice. GH decreased relative fat mass in lit/lit mice and had no effect in GH-intact mice. Treatment with GHS, b ut not GH, increased serum leptin and food intake in GH-intact mice. Thus, GHSs increase body fat by GH-independent mechanisms that may include increa sed feeding. (C) 2001 Academic Press.