Ghrelin improves body weight loss and skeletal muscle catabolism associated with angiotensin II-induced cachexia in mice.

Abstract

Ghrelin is a gastric peptide that regulates energy homeostasis. Angiotensin II (Ang II) is known to induce body weight loss and skeletal muscle catabolism through the ubiquitin-proteasome pathway. In this study, we investigated the effects of ghrelin on body weight and muscle catabolism in mice treated with Ang II. The continuous subcutaneous administration of Ang II to mice for 6 days resulted in cardiac hypertrophy and significant decreases in body weight gain, food intake, food efficiency, lean mass, and fat mass. In the gastrocnemius muscles of Ang II-treated mice, the levels of insulin-like growth factor 1 (IGF-1) were decreased, and the levels of mRNA expression of catabolic factors were increased. Although the repeated subcutaneous injections of ghrelin (1.0mg/kg, twice daily for 5 days) did not affect cardiac hypertrophy, they resulted in significant body weight gains and improved food efficiencies and tended to increase both lean and fat mass in Ang II-treated mice. Ghrelin also ameliorated the decreased IGF-1 levels and the increased mRNA expression levels of catabolic factors in the skeletal muscle. IGF-1 mRNA levels in the skeletal muscle significantly decreased 24h after Ang II infusion, and this was reversed by two subcutaneous injections of ghrelin. In C2C12-derived myocytes, the dexamethasone-induced mRNA expression of atrogin-1 was decreased by IGF-1 but not by ghrelin. In conclusion, we demonstrated that ghrelin improved body weight loss and skeletal muscle catabolism in mice treated with Ang II, possibly through the early restoration of IGF-1 mRNA in the skeletal muscle and the amelioration of nutritional status.

• Authors: Masako Sugiyama, Akira Yamaki, Mayumi Furuya, Norio Inomata, Yoshiharu Minamitake, Kazuhiro Ohsuye, Kenji Kangawa
• Journal: Regulatory peptides (Regul Pept) Vol. 178 Issue 1-3 Pg. 21-8 (Oct 10 2012) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 22750276 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Forkhead Box Protein O1
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• FoxO3 protein, mouse
• Foxo1 protein, mouse
• Ghrelin
• Muscle Proteins
• Tripartite Motif Proteins
• insulin-like growth factor-1, mouse
• Angiotensin II
• Insulin-Like Growth Factor I
• Fbxo32 protein, mouse
• SKP Cullin F-Box Protein Ligases
• Trim63 protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Adiposity (drug effects)
• Angiotensin II
• Animals
• Cachexia (chemically induced, drug therapy)
• Cell Line
• Feeding Behavior (drug effects)
• Forkhead Box Protein O1
• Forkhead Box Protein O3
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Expression (drug effects)
• Ghrelin (administration & dosage)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Mice
• Muscle Cells (drug effects, metabolism)
• Muscle Proteins (genetics, metabolism)
• Muscle, Skeletal (drug effects, metabolism, pathology)
• SKP Cullin F-Box Protein Ligases (genetics, metabolism)
• Tripartite Motif Proteins
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Weight Loss (drug effects)