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Title 

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

Authors 

M S LeeH J HanS Y HanI Y KimS ChaeC S LeeS E KimS G YoonJ W ParkJ H KimS ShinM JeongA KoH Y LeeKyoung Jin OhY H LeeKwang-Hee BaeS H KooJ W KimJ K SeongD HwangJ Song

Publisher 

Nature Publishing Group

Issue Date 

2018

Citation 

Nature Communications

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.

ISSN 

2041-1723

Link 

http://dx.doi.org/10.1038/s41467-018-05721-4

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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