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Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation

Authors
 Min-Sik Lee  ;  Hyun-Ji Han  ;  Su Yeon Han  ;  Il Young Kim  ;  Sehyun Chae  ;  Choong-Sil Lee  ;  Sung Eun Kim  ;  Seul Gi Yoon  ;  Jun-Won Park  ;  Jung-Hoon Kim  ;  Soyeon Shin  ;  Manhyung Jeong  ;  Aram Ko  ;  Ho-Young Lee  ;  Kyoung-Jin Oh  ;  Yun-Hee Lee  ;  Kwang-Hee Bae  ;  Seung-Hoi Koo  ;  Jea-woo Kim  ;  Je Kyung Seong  ;  Daehee Hwang  ;  Jaewhan Song 
Citation
 Nature Communications, Vol.9 : 3404, 2018 
Journal Title
 Nature Communications 
Issue Date
2018
Abstract
AMP-activated protein kinase (AMPK) plays a key role in controlling energy metabolism in response to physiological and nutritional status. Although AMPK activation has been proposed as a promising molecular target for treating obesity and its related comorbidities, the use of pharmacological AMPK activators has been met with contradictory therapeutic challenges. Here we show a regulatory mechanism for AMPK through its ubiquitination and degradation by the E3 ubiquitin ligase makorin ring finger protein 1 (MKRN1). MKRN1 depletion promotes glucose consumption and suppresses lipid accumulation due to AMPK stabilisation and activation. Accordingly, MKRN1-null mice show chronic AMPK activation in both liver and adipose tissue, resulting in significant suppression of diet-induced metabolic syndrome. We demonstrate also its therapeutic effect by administering shRNA targeting MKRN1 into obese mice that reverses non-alcoholic fatty liver disease. We suggest that ubiquitin-dependent AMPK degradation represents a target therapeutic strategy for metabolic disorders.
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DOI
10.1038/s41467-018-05721-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
김재우(Kim, Jae Woo) ORCID logo https://orcid.org/0000-0001-5456-9495
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163313
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