Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation

Masanori Tamaki, Kazutoshi Miyashita, Aika Hagiwara, Shu Wakino, Hiroyuki Inoue, Kentaro Fujii, Chikako Fujii, Sho Endo, Asuka Uto, Masanori Mitsuishi, Masaaki Sato, Toshio Doi, Hiroshi Itoh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)S47-S51
JournalEndocrine Journal
Volume64
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Chronic kidney disease
  • Ghrelin
  • Mitochondria
  • Physical performance
  • Sarcopenia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Tamaki, M., Miyashita, K., Hagiwara, A., Wakino, S., Inoue, H., Fujii, K., Fujii, C., Endo, S., Uto, A., Mitsuishi, M., Sato, M., Doi, T., & Itoh, H. (2017). Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation. Endocrine Journal, 64, S47-S51. https://doi.org/10.1507/endocrj.64.S47