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

6 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

Fingerprint

Sarcopenia
Ghrelin
Methylation
Muscles
Muscle Strength
Chronic Renal Insufficiency
Skeletal Muscle
Muscle Mitochondrion
Polymerase Chain Reaction
Cytosine
Organelle Biogenesis
Mitochondrial DNA
Genetic Promoter Regions
Epigenomics
Base Pairing
Oxygen
Mortality

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation. / Tamaki, Masanori; Miyashita, Kazutoshi; Hagiwara, Aika; Wakino, Shu; Inoue, Hiroyuki; Fujii, Kentaro; Fujii, Chikako; Endo, Sho; Uto, Asuka; Mitsuishi, Masanori; Sato, Masaaki; Doi, Toshio; Itoh, Hiroshi.

In: Endocrine Journal, Vol. 64, 01.01.2017, p. S47-S51.

Research output: Contribution to journalArticle

Tamaki, Masanori ; Miyashita, Kazutoshi ; Hagiwara, Aika ; Wakino, Shu ; Inoue, Hiroyuki ; Fujii, Kentaro ; Fujii, Chikako ; Endo, Sho ; Uto, Asuka ; Mitsuishi, Masanori ; Sato, Masaaki ; Doi, Toshio ; Itoh, Hiroshi. / Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation. In: Endocrine Journal. 2017 ; Vol. 64. pp. S47-S51.
@article{2c351028976545fbb685b9dd240e72e3,
title = "Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation",
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.",
keywords = "Chronic kidney disease, Ghrelin, Mitochondria, Physical performance, Sarcopenia",
author = "Masanori Tamaki and Kazutoshi Miyashita and Aika Hagiwara and Shu Wakino and Hiroyuki Inoue and Kentaro Fujii and Chikako Fujii and Sho Endo and Asuka Uto and Masanori Mitsuishi and Masaaki Sato and Toshio Doi and Hiroshi Itoh",
year = "2017",
month = "1",
day = "1",
doi = "10.1507/endocrj.64.S47",
language = "English",
volume = "64",
pages = "S47--S51",
journal = "Endocrine Journal",
issn = "0918-8959",
publisher = "Japan Endocrine Society",

}

TY - JOUR

T1 - Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation

AU - Tamaki, Masanori

AU - Miyashita, Kazutoshi

AU - Hagiwara, Aika

AU - Wakino, Shu

AU - Inoue, Hiroyuki

AU - Fujii, Kentaro

AU - Fujii, Chikako

AU - Endo, Sho

AU - Uto, Asuka

AU - Mitsuishi, Masanori

AU - Sato, Masaaki

AU - Doi, Toshio

AU - Itoh, Hiroshi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Ghrelin

KW - Mitochondria

KW - Physical performance

KW - Sarcopenia

UR - http://www.scopus.com/inward/record.url?scp=85043298651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043298651&partnerID=8YFLogxK

U2 - 10.1507/endocrj.64.S47

DO - 10.1507/endocrj.64.S47

M3 - Article

C2 - 28652544

AN - SCOPUS:85043298651

VL - 64

SP - S47-S51

JO - Endocrine Journal

JF - Endocrine Journal

SN - 0918-8959

ER -