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A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes

Authors
 Hyejin Lim  ;  Yu-Mi Lim  ;  Kook Hwan Kim  ;  Young Eui Jeon  ;  Kihyoun Park  ;  Jinyoung Kim  ;  Hui-Yun Hwang  ;  Dong Jin Lee  ;  Haushabhau Pagire  ;  Ho Jeong Kwon  ;  Jin Hee Ahn  ;  Myung-Shik Lee 
Citation
 Nature Communications, Vol.9(1) : 1438, 2018 
Journal Title
 Nature Communications 
Issue Date
2018
Abstract
Autophagy is a critical regulator of cellular homeostasis, dysregulation of which is associated with diverse diseases. Here we show therapeutic effects of a novel autophagy enhancer identified by high-throughput screening of a chemical library against metabolic syndrome. An autophagy enhancer increases LC3-I to LC3-II conversion without mTOR inhibition. MSL, an autophagy enhancer, activates calcineurin, and induces dephosphorylation/nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy gene expression. MSL accelerates intracellular lipid clearance, which is reversed by lalistat 2 or Tfeb knockout. Its administration improves the metabolic profile of ob/ob mice and ameliorates inflammasome activation. A chemically modified MSL with increased microsomal stability improves the glucose profile not only of ob/ob mice but also of mice with diet-induced obesity. Our data indicate that our novel autophagy enhancer could be a new drug candidate for diabetes or metabolic syndrome with lipid overload.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162321
Files in This Item:
T201801385.pdf Download
DOI
10.1038/s41467-018-03939-w
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
Yonsei Authors
김국환(Kim, Kook Hwan)
이명식(Lee, Myung Shik)
임혜진(Lim, Hyejin)
전영의(Jeon, Yeong Eui)
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