Amelioration of obesity-induced diabetes by a novel autophagy enhancer
Authors:Hyejin Lim1 and Myung-Shik Lee1
1 Severance Biomedical Science Institute and Dept. of Medicine, Yonsei University College of Medicine, Seoul, Korea.
Keywords:
Tfeb, calcineurin, lysosome, Ca2+, phosphatase.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest related to this work.
Please cite this article as:
Hyejin Lim and Myung-Shik Lee (2018). Amelioration of obesity-induced diabetes by a novel autophagy enhancer. Cell Stress 2(7): 181-183. doi: 10.15698/cst2018.07.146
© 2018 Lim and Lee. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Autophagy insufficiency due to aging, high-fat injury or genetic predisposition could be a factor in the progression of metabolic syndrome and diabetes. On the other hand, autophagy enhancement may have beneficial metabolic impact on in vivo metabolism of obese subjects. To identify novel, autophagy enhancer small molecules, we screened a chemical library using a Renilla-LC3-based luciferase assay [Lim et al. Nat Commun 9:1438]. Of the >7000 tested substances, one chemical compound, termed MSL (4-(4-fluorophenyl)sulfonyl-5-methylthio-2-phenyloxazole), (i) enhanced autophagic activity through Tfeb activation, (ii) expedited lipid clearance, probably through lipophagy, and (iii) reduced inflammasome activation through amelioration of mitochondrial dysfunction both in vitro and in vivo, leading to improved metabolic profile of mice with genetic or diet-induced obesity.