FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis

Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection wit...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xiaobo, Huang, Ning, Yang, Min, Wei, Dandan, Tai, Haoran, Han, Xiaojuan, Gong, Hui, Zhou, Jiao, Qin, Jianqiong, Wei, Xiawei, Chen, Honghan, Fang, Tingting, Xiao, Hengyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386528/
https://www.ncbi.nlm.nih.gov/pubmed/28333151
http://dx.doi.org/10.1038/cddis.2017.122
_version_ 1782520782455308288
author Wang, Xiaobo
Huang, Ning
Yang, Min
Wei, Dandan
Tai, Haoran
Han, Xiaojuan
Gong, Hui
Zhou, Jiao
Qin, Jianqiong
Wei, Xiawei
Chen, Honghan
Fang, Tingting
Xiao, Hengyi
author_facet Wang, Xiaobo
Huang, Ning
Yang, Min
Wei, Dandan
Tai, Haoran
Han, Xiaojuan
Gong, Hui
Zhou, Jiao
Qin, Jianqiong
Wei, Xiawei
Chen, Honghan
Fang, Tingting
Xiao, Hengyi
author_sort Wang, Xiaobo
collection PubMed
description Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice. Significantly, FTO-promoted myogenic differentiation was dependent on its m6A demethylase activity. Mechanically, we found that FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) gene, together with declined ATP level. Moreover, the involvement of mTOR-PGC-1α pathway in the connection between FTO and muscle differentiation is displayed, since the expression of FTO affected the activity of mTOR and rapamycin blocked FTO-induced PGC-1α transcription, along with the parallel alteration pattern of FTO expression and mTOR phosphorylation during myoblasts differentiation. Summarily, our findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation and a new insight to study the physiologic significance of RNA methylation.
format Online
Article
Text
id pubmed-5386528
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-53865282017-04-27 FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis Wang, Xiaobo Huang, Ning Yang, Min Wei, Dandan Tai, Haoran Han, Xiaojuan Gong, Hui Zhou, Jiao Qin, Jianqiong Wei, Xiawei Chen, Honghan Fang, Tingting Xiao, Hengyi Cell Death Dis Original Article Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice. Significantly, FTO-promoted myogenic differentiation was dependent on its m6A demethylase activity. Mechanically, we found that FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) gene, together with declined ATP level. Moreover, the involvement of mTOR-PGC-1α pathway in the connection between FTO and muscle differentiation is displayed, since the expression of FTO affected the activity of mTOR and rapamycin blocked FTO-induced PGC-1α transcription, along with the parallel alteration pattern of FTO expression and mTOR phosphorylation during myoblasts differentiation. Summarily, our findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation and a new insight to study the physiologic significance of RNA methylation. Nature Publishing Group 2017-03 2017-03-23 /pmc/articles/PMC5386528/ /pubmed/28333151 http://dx.doi.org/10.1038/cddis.2017.122 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Wang, Xiaobo
Huang, Ning
Yang, Min
Wei, Dandan
Tai, Haoran
Han, Xiaojuan
Gong, Hui
Zhou, Jiao
Qin, Jianqiong
Wei, Xiawei
Chen, Honghan
Fang, Tingting
Xiao, Hengyi
FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title_full FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title_fullStr FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title_full_unstemmed FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title_short FTO is required for myogenesis by positively regulating mTOR-PGC-1α pathway-mediated mitochondria biogenesis
title_sort fto is required for myogenesis by positively regulating mtor-pgc-1α pathway-mediated mitochondria biogenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386528/
https://www.ncbi.nlm.nih.gov/pubmed/28333151
http://dx.doi.org/10.1038/cddis.2017.122
work_keys_str_mv AT wangxiaobo ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT huangning ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT yangmin ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT weidandan ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT taihaoran ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT hanxiaojuan ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT gonghui ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT zhoujiao ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT qinjianqiong ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT weixiawei ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT chenhonghan ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT fangtingting ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis
AT xiaohengyi ftoisrequiredformyogenesisbypositivelyregulatingmtorpgc1apathwaymediatedmitochondriabiogenesis