Description

AOD9604, a modified peptide from human growth hormone, has demonstrated various therapeutic benefits, including in weight loss, heart disease, osteoarthritis, and metabolic syndrome. It promotes fat breakdown and inhibits fat formation in animal studies. Both human GH and AOD9604 induce weight loss and enhance lipolytic sensitivity in obese mice, potentially through interactions with beta(3)-adrenergic receptors (beta(3)-AR). While AOD9604 increases beta(3)-AR expression, its lipolytic effects are not directly mediated by this receptor. In acute experiments, AOD9604 also increased energy expenditure and fat oxidation in beta(3)-AR knock-out mice. (1)

In a rabbit model of collagenase-induced knee osteoarthritis (OA), intra-articular injections of AOD9604, with or without hyaluronic acid (HA), were evaluated. Groups treated with AOD9604 alone or in combination with HA showed better cartilage regeneration and reduced lameness compared to those receiving saline or HA alone. The combined treatment of AOD9604 and HA was the most effective, indicating that AOD9604 enhances cartilage repair, particularly when used with HA. (2)

Both human growth hormone (hGH) and its lipolytic fragment AOD9604 can induce weight loss and increase lipolytic sensitivity in obese mice after 14 days of treatment. This effect is associated with increased expression of beta(3)-adrenergic receptors (beta(3)-AR), which are crucial for fat breakdown. Both hGH and AOD9604 raised beta(3)-AR RNA levels in obese mice to levels seen in lean mice. However, the lipolytic effects were absent in beta(3)-AR knock-out mice, indicating that beta(3)-AR is important for these actions. Despite this, AOD9604 increased energy expenditure and fat oxidation in beta(3)-AR knock-out mice in an acute setting. Thus, while hGH and AOD9604 enhance beta(3)-AR expression, their lipolytic actions are not directly mediated by beta(3)-AR. (3)

(1) Heffernan, M., Summers, R. J., Thorburn, A., Ogru, E., Gianello, R., Jiang, W. J., & Ng, F. M. (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. https://doi.org/10.1210/endo.142.12.8522

(2) Kwon, D. R., & Park, G. Y. (2015). Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Annals of clinical and laboratory science, 45(4), 426–432.

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