GH Secretagogues Boost Body Fat Independently of Growth Hormone in Mice

Growth hormone secretagogues (GHSs) are known to stimulate growth hormone (GH) secretion, which typically has lipolytic (fat-burning) effects. However, it's unclear if GHSs always lead to fat loss or if they might have GH-independent effects on adiposity (body fat). This study investigates whether GHSs can increase body fat even in the absence of GH.

In both GH-deficient (lit/lit) and GH-intact (+/lit) mice, ipamorelin induced a small but statistically significant 15% increase in body weight by 2 weeks, an effect that did not further augment even after 9 weeks of continued treatment. Crucially, ipamorelin consistently increased fat pad weights relative to total body weight in both lit/lit and +/lit mouse groups, indicating a direct impact on fat accumulation. A key finding was that two weeks of GHS treatment (ipamorelin or GHRP-6) significantly increased relative body fat, quantified by DEXA, in GH-intact mice, whereas GH treatment itself decreased relative fat mass in lit/lit mice and had no significant effect in GH-intact mice. Furthermore, GHS treatment, but not GH, led to an increase in serum leptin (a hormone that signals satiety and regulates energy balance) and a notable increase in food intake in GH-intact mice, suggesting a potential mechanism for the observed adiposity.