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Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine.
MedLine Citation:
PMID:  23202295     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle-specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.
Authors:
Kook Hwan Kim; Yeon Taek Jeong; Hyunhee Oh; Seong Hun Kim; Jae Min Cho; Yo-Na Kim; Su Sung Kim; Do Hoon Kim; Kyu Yeon Hur; Hyoung Kyu Kim; Taehee Ko; Jin Han; Hong Lim Kim; Jin Kim; Sung Hoon Back; Masaaki Komatsu; Hsiuchen Chen; David C Chan; Morichika Konishi; Nobuyuki Itoh; Cheol Soo Choi; Myung-Shik Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-02
Journal Detail:
Title:  Nature medicine     Volume:  -     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. [2] Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
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