The fat-reducing effects of the growth hormone peptide AOD9604 in mice

This study conducted by Frank Ng and colleagues investigated AOD-9604, a peptide fragment corresponding to the C-terminal region (amino acids 177-191) of human growth hormone (hGH), modified to retain the lipolytic properties of GH without its diabetogenic and growth-promoting effects. AOD-9604 was administered to obese mice (ob/ob model) intraperitoneally over varying treatment periods.

The results demonstrated that AOD-9604 promoted significant body fat reduction in a dose-dependent manner. Crucially, unlike intact growth hormone, the peptide did not alter blood glucose levels or IGF-1 (insulin-like growth factor type 1) concentrations, two parameters that typically rise with GH administration and are associated with metabolic risks such as insulin resistance.

The proposed mechanism involves stimulation of lipolysis (fat breakdown) and inhibition of lipogenesis (new fat formation) in adipose tissue, without activating GH receptors in the same way as the intact molecule. This gives AOD-9604 a particularly interesting selective lipolytic profile from a therapeutic standpoint.

This study was fundamental in establishing that the metabolic effects of GH can be dissociated, isolating fat-reducing activity in a small, safe peptide fragment. The findings paved the way for subsequent clinical studies in humans and led to the classification of AOD-9604 as a GRAS (Generally Recognized as Safe) supplement by the FDA for oral use.