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AOD-9604, the lipolytic fragment of human growth hormone, in adipocyte metabolism

Endocrinology · 2001AOD-9604Research summary

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.

Overview

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.

References

Peer-reviewed sources for the research summarised above. Vivo summarises published, third-party science and does not conduct or sponsor this research.

  1. Heffernan M, Summers RJ, Thorburn A, et al. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology;142(12):5182-5189. View source ↗
  2. Ng FM, Jiang WJ, Gianello R, Pitt S, Roupas P (2000). Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. J Mol Endocrinol;25(3):287-298. View source ↗
  3. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM (2000). Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Am J Physiol Endocrinol Metab;279(3):E501-E507. View source ↗
  4. Heffernan MA, Thorburn AW, Fam B, et al. (2001). Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord;25(10):1442-1449. View source ↗
  5. Ng FM, Sun J, Sharma L, et al. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res;53(6):274-278. View source ↗
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