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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Lee MS,Han HJ,Han SY,Kim IY,Chae S,Lee CS,Kim SE,Yoon SG,Park JW,Kim JH,Shin S,Jeong M,Ko A,Lee HY,Oh KJ,Lee YH,Bae KH,Koo SH,Kim JW,Seong JK,Hwang D,Song Jdoi
10.1038/s41467-018-05721-4subject
Has Abstractpub_date
2018-08-24 00:00:00pages
3404issue
1issn
2041-1723pii
10.1038/s41467-018-05721-4journal_volume
9pub_type
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