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
- Issue Date
- 24-8월-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.9
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 9
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/73730
- DOI
- 10.1038/s41467-018-05721-4
- ISSN
- 2041-1723
- 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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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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