The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice andβ 3-AR Knock-Out Mice

• Published in: Endocrinology (Philadelphia) 2001-12, Vol.142 (12), p.5182-5189
• Main Authors: Heffernan, Mark, Summers, Roger J, Thorburn, Anne, Ogru, Esra, Gianello, Robert, Jiang, Woei-Jia, Ng, Frank M
• Format: Article
• Language: English
• Subjects: Adipocytes; Adrenergic receptors; Body fat; Body weight; Body weight loss; C-Terminus; Energy expenditure; Gene expression; Lipid metabolism; Lipids; Lipolysis; Oxidation; Receptors (physiology); Weight loss
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.142.12.8522

Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice. One mechanism by which this may occur is through an interaction with theβ -adrenergic pathway, particularly with theβ 3-adrenergic receptors (β3-AR). Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression ofβ 3-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of β3-AR RNA in obese mice to levels comparable with those in lean mice. The importance ofβ 3-AR was verified when long-term treatment with hGH and AOD9604 in β3-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in theβ 3-AR knock-out mice. In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the β3-AR although both compounds increase β3-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.