Ghrelin improves body weight loss and skeletal muscle catabolism associated with angiotensin II-induced cachexia in mice
| Autor: | Norio Inomata, Masako Sugiyama, Akira Yamaki, Yoshiharu Minamitake, Mayumi Furuya, Kenji Kangawa, Kazuhiro Ohsuye |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Cachexia Physiology Ubiquitin-Protein Ligases Clinical Biochemistry Gene Expression Muscle Proteins Biochemistry Energy homeostasis Cell Line Tripartite Motif Proteins Cellular and Molecular Neuroscience Mice Endocrinology Internal medicine Weight Loss medicine Myocyte Animals Humans Insulin-Like Growth Factor I Muscle Skeletal Adiposity Muscle Cells SKP Cullin F-Box Protein Ligases Catabolism Chemistry Forkhead Box Protein O1 Angiotensin II digestive oral and skin physiology Forkhead Box Protein O3 Skeletal muscle Forkhead Transcription Factors Feeding Behavior medicine.disease Ghrelin medicine.anatomical_structure Lean body mass hormones hormone substitutes and hormone antagonists |
| Zdroj: | Regulatory peptides. 178(1-3) |
| ISSN: | 1873-1686 |
| Popis: | 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 (1.0 mg/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 24 h 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. |
| Databáze: | OpenAIRE |
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