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

 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 
 NATURE COMMUNICATIONS, Vol.9(1) : 1438, 2018 
Journal Title
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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.
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Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kook Hwan(김국환)
Kim, Jinyoung(김진영)
Lee, Myung Shik(이명식) ORCID logo https://orcid.org/0000-0003-3292-1720
Lim, Hyejin(임혜진)
Jeon, Yeong Eui(전영의) ORCID logo https://orcid.org/0000-0001-6316-4107
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