Effect of intranasally administered MSH/ACTH 4–10 on skeletal muscle and adipose tissue metabolism in young men

Melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. Prolonged administration of the melanocortin core fragment alpha-MSH was found to reduce body weight in animals and humans by increasing energy expenditure and by reducing food intake. The aim of this study was to investigate an additional effect of intranasally administered alpha-MSH on local lipolysis in peripheral tissues such as skeletal muscle or subcutaneous fat.

After an overnight fast ten healthy and normal weight volunteers received either 5mg alpha MSH or placebo intranasally in a double-blinded randomized order on two consecutive days. Microdialysis for the detection of glycerol, glucose and lactate was performed in skeletal muscle and subcutaneous adipose tissue.

150 minutes after intranasal application of 5mg alpha MSH glycerol in skeletal muscle increased by Δ=49.4±31.6%, while the administration placebo had no effect (p<0.05). In parallel glycerol in subcutaneous adipose tissue also increased (Δ=49.0±29.5%), however this effect became not significant compared to placebo. Interstitial lactate and glucose did not show any significant changes, neither in muscle nor in adipose tissue.

Previous experiments have shown that intranasal administration of 5mg alpha MSH yields sufficient accumulation in the cerebro-spinal fluid. By using this method we could show that alpha MSH increases lipolysis in peripheral tissues. However, this effect is only significant in skeletal muscle and probably contributes only minimally to its overall anorectic effects in humans.