Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation
Autor: | Masaaki Sato, Kentaro Fujii, Hiroyuki Inoue, Masanori Mitsuishi, Masanori Tamaki, Shu Wakino, Toshio Doi, Asuka Uto, Kazutoshi Miyashita, Hiroshi Itoh, Sho Endo, Chikako Fujii, Aika Hagiwara |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Mitochondrial DNA Sarcopenia Endocrinology Diabetes and Metabolism 030232 urology & nephrology Peroxisome proliferator-activated receptor Mitochondrion Nephrectomy Epigenesis Genetic 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Internal medicine Physical Conditioning Animal medicine Animals Muscle Strength Muscle Skeletal chemistry.chemical_classification business.industry Skeletal muscle medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Ghrelin Mitochondria Muscle Disease Models Animal 030104 developmental biology medicine.anatomical_structure Real-time polymerase chain reaction Mitochondrial biogenesis chemistry Physical Endurance business |
Zdroj: | Endocrine journal. 64 |
ISSN: | 1348-4540 |
Popis: | Chronic kidney disease (CKD) impairs physical performance in humans, which leads to a risk of all-cause mortality. In our previous study, we demonstrated that a reduction in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized CKD model mice. Because ghrelin administration has been reported to enhance oxygen utilization in skeletal muscle, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6 nephrectomized C57Bl/6 mice, focusing on the epigenetic modification of peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. The mice were intraperitoneally administered acylated ghrelin (0.1 nmol/gBW; three times per week) for a month. Muscle strength and exercise endurance were measured by using a dynamometer and treadmill, respectively. Mitochondrial DNA copy number was determined by quantitative PCR. The methylation levels of the cytosine residue at 260 base pairs upstream of the translation initiation point (C-260) of PGC-1α, which has been demonstrated to decrease the expression, was evaluated by methylation-specific PCR and bisulfite genomic sequencing methods after the ghrelin administration. Ghrelin administration improved both muscle strength and exercise endurance in the mice and was associated with an increase in muscle mass and muscle mitochondrial content. Ghrelin administration decreased the methylation ratio of C-260 of PGC-1α in the skeletal muscle and increased the expression. Therefore, ghrelin administration effectively reduced the physical decline in 5/6 nephrectomized mice and was accompanied with an increased mitochondrial content through de-methylation of the promoter region of PGC-1α in the muscle. |
Databáze: | OpenAIRE |
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