AOD-9604 is a synthetic fragment of the C-terminus of human growth hormone, studied in preclinical models for its effect on fat metabolism independent of the growth-hormone receptor.
AOD-9604 is a synthetic analogue of the C-terminal lipolytic domain of human growth hormone (hGH fragment 176-191), studied for its actions on fat metabolism in adipose tissue. Studies report that this fragment retains the lipolytic (fat-breakdown) and antilipogenic (reduced fat synthesis) activity of the intact hormone while lacking the effects mediated through the classical growth hormone receptor and IGF-1 axis. In rodent models it did not induce the hyperglycemia or insulin resistance associated with full-length hGH.
In isolated rat adipose tissue, research suggests the peptide stimulates hormone-sensitive lipase and inhibits acetyl-CoA carboxylase, a key lipogenic enzyme. In rodent models of obesity, chronic administration reduced body-weight gain, decreased adipocyte size, and increased fat oxidation. Mechanistic work indicates involvement of beta-adrenergic signalling: in obese mice the fragment restored suppressed beta-3 adrenergic receptor expression, and beta-3 receptor knockout mice were unresponsive to its lipolytic effect. This evidence is largely preclinical, with early human data producing inconsistent outcomes.
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