論文 - 詳細
| RRC ID | 67780 |
|---|---|
| 著者 | Tamaki M, Hagiwara A, Miyashita K, Wakino S, Inoue H, Fujii K, Fujii C, Sato M, Mitsuishi M, Muraki A, Hayashi K, Doi T, Itoh H. |
| タイトル | Improvement of Physical Decline Through Combined Effects of Muscle Enhancement and Mitochondrial Activation by a Gastric Hormone Ghrelin in Male 5/6Nx CKD Model Mice. |
| ジャーナル | Endocrinology |
| Abstract |
Because a physical decline correlates with an increased risk of a wide range of disease and morbidity, an improvement of physical performance is expected to bring significant clinical benefits. The primary cause of physical decline in 5/6 nephrectomized (5/6Nx) chronic kidney disease model mice has been regarded as a decrease in muscle mass; however, our recent study showed that a decrease in muscle mitochondria plays a critical role. In the present study, we examined the effects of a gastric hormone ghrelin, which has been reported to promote muscle mitochondrial oxidation, on the physical decline in the chronic kidney disease model mice, focusing on the epigenetic modulations of a mitochondrial activator gene, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Ghrelin treatment improved a decline in exercise endurance of 5/6Nx mice, associated with an increase in both of the muscle mass and mitochondrial amount. The expression level of PGC-1α was decreased in the skeletal muscle of 5/6Nx mice, which was associated with an increase in the methylation ratio of the cytosine residue at 260 base pairs upstream of the initiation point. Conversely, ghrelin treatment de-methylated the cytosine residue and increased the expression of PGC-1α. A representative muscle anabolic factor, IGF-1, did not affect the expression of PGC-1α and muscle mitochondrial amount, although it increased muscle mass. As a result, IGF-1 treatment in 5/6Nx mice did not increase the decreased exercise endurance as effectively as ghrelin treatment did. These findings indicate an advantage of ghrelin treatment for a recovery of physical decline. |
| 巻・号 | 156(10) |
| ページ | 3638-48 |
| 公開日 | 2015-10-1 |
| DOI | 10.1210/en.2015-1353 |
| PMID | 26241123 |
| MeSH | AMP-Activated Protein Kinases / metabolism Animals Blotting, Western Cell Line DNA Methylation / drug effects Disease Models, Animal Electron Transport Complex IV / genetics Electron Transport Complex IV / metabolism Gene Expression / drug effects Ghrelin / blood Ghrelin / genetics Ghrelin / pharmacology* Male Mice, Inbred C57BL Mitochondria, Muscle / drug effects* Mitochondria, Muscle / genetics Mitochondria, Muscle / metabolism Motor Activity / drug effects Muscle Weakness / drug therapy* Muscle Weakness / genetics Muscle Weakness / metabolism Muscle, Skeletal / drug effects* Muscle, Skeletal / metabolism Muscle, Skeletal / pathology Myoblasts / drug effects Myoblasts / metabolism Nephrectomy Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha RNA Interference Receptors, Ghrelin / genetics Receptors, Ghrelin / metabolism Renal Insufficiency, Chronic / complications* Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 3.934 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |