The melanocortin system plays a significant role in the hypothalamic regulation of body weight and energy expenditure. Prolonged central administration of the melanocortin receptor 4 (MC-4) agonist ACTH(4-10) reduces body weight in animals and humans by increasing energy expenditure and by reducing food intake. The aim of this study was to investigate the effect of intranasally administered alpha-MSH on local lipolysis in subcutaneous adipose tissue and on sympathetic nerve activity (SNA) to the muscle (MSNA). After an overnight fast ten healthy and normal weight volunteers received either 10 mg ACTH(4-10) or placebo intranasally in a double-blind randomized fashion on two consecutive days. Microdialysis for the detection of glycerol, glucose and lactate was performed in abdominal subcutaneous adipose tissue; simultaneously we recorded SNA to the lateral femoral nerve. After intranasal application of 10 mg ACTH(4-10) glycerol in adipose tissue increased and was significantly higher after 45 min when compared to placebo (Δbaseline=53.4±19.3% for ACTH(4-10), 22.2±14.1% for placebo, P<0.05). Interstitial lactate and glucose did not show any significant changes. Basal MSNA was not different after ACTH(4-10) or placebo, however, intravenous nitroprusside increased burst frequency by 569±69% after ACTH(4-10) treatment but only by 315±64% after placebo. This difference was statistically significant (P=0.012). Previous experiments in humans have shown that intranasal administration of ACTH(4-10) yields sufficient concentrations in the cerebrospinal fluid. In our experiments, intranasally (centrally) administered ACTH(4-10) stimulates lipolysis in peripheral organs like adipose tissue. This central effect of the MC-4 agonist might be mediated through autonomous nerves since lipolysis was associated with an increase of baroreceptor reflex sensitivity which in turn could reflect an activation of the central sympathetic nervous system.
03 - 07 May 2008
European Society of Endocrinology