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

Masanori Tamaki, Aika Hagiwara, Kazutoshi Miyashita, Shu Wakino, Hiroyuki Inoue, Kentaro Fujii, Chikako Fujii, Masaaki Sato, Masanori Mitsuishi, Ayako Muraki, Koichi Hayashi, Toshio Doi, Hiroshi Itoh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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-α 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 demethylated 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.

Original languageEnglish
Pages (from-to)3638-3648
Number of pages11
JournalEndocrinology
Volume156
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

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Ghrelin
Stomach
Hormones
Muscles
Cytosine
Insulin-Like Growth Factor I
Chronic Renal Insufficiency
Muscle Mitochondrion
Peroxisome Proliferator-Activated Receptors
Mitochondrial Genes
Epigenomics
Base Pairing
Methylation
Skeletal Muscle
Morbidity

ASJC Scopus subject areas

  • Endocrinology

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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. / Tamaki, Masanori; Hagiwara, Aika; Miyashita, Kazutoshi; Wakino, Shu; Inoue, Hiroyuki; Fujii, Kentaro; Fujii, Chikako; Sato, Masaaki; Mitsuishi, Masanori; Muraki, Ayako; Hayashi, Koichi; Doi, Toshio; Itoh, Hiroshi.

In: Endocrinology, Vol. 156, No. 10, 01.10.2015, p. 3638-3648.

Research output: Contribution to journalArticle

Tamaki, Masanori ; Hagiwara, Aika ; Miyashita, Kazutoshi ; Wakino, Shu ; Inoue, Hiroyuki ; Fujii, Kentaro ; Fujii, Chikako ; Sato, Masaaki ; Mitsuishi, Masanori ; Muraki, Ayako ; Hayashi, Koichi ; Doi, Toshio ; Itoh, Hiroshi. / 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. In: Endocrinology. 2015 ; Vol. 156, No. 10. pp. 3638-3648.
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