Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation
SCIE
SCOPUS
- Title
- Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation
- Authors
- Lee, Min-Sik; Han, Hyun-Ji; Han, Su Yeon; Kim, Il Young; Chae, Sehyun; Lee, Choong-Sil; Kim, Sung Eun; Yoon, Seul Gi; Park, Jun-Won; Kim, Jung-Hoon; Shin, Soyeon; Jeong, Manhyung; Ko, Aram; Lee, Ho-Young; Oh, Kyoung-Jin; Lee, Yun-Hee; Bae, Kwang-Hee; Koo, Seung-Hoi; Kim, Jea-woo; Seong, Je Kyung; Hwang, Daehee; Song, Jaewhan
- Date Issued
- 2018-08
- Publisher
- Nature Publishing Group
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/120845
- DOI
- 10.1038/s41467-018-05721-4
- Article Type
- Article
- Citation
- Nature Communications, vol. 9, no. 1, 2018-08
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.