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.

Abstract

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 the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-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 of beta(3)-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-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 the beta(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 beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.

• Authors: M Heffernan, R J Summers, A Thorburn, E Ogru, R Gianello, W J Jiang, F M Ng
• Journal: Endocrinology (Endocrinology) Vol. 142 Issue 12 Pg. 5182-9 (Dec 2001) ISSN: 0013-7227 [Print] United States
• PMID: 11713213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AOD 9604
• Peptide Fragments
• RNA, Messenger
• Receptors, Adrenergic, beta-3
• Human Growth Hormone
• Somatostatin

Topics

• Adipose Tissue (drug effects, pathology)
• Animals
• Body Weight (drug effects)
• Energy Metabolism (drug effects)
• Human Growth Hormone (pharmacology)
• Humans
• Lipid Metabolism
• Lipolysis (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout (genetics)
• Obesity (metabolism, pathology)
• Oxidation-Reduction (drug effects)
• Peptide Fragments (pharmacology)
• RNA, Messenger (metabolism)
• Receptors, Adrenergic, beta-3 (deficiency, genetics, physiology)
• Reference Values
• Somatostatin (pharmacology)
• Time Factors