MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN

Jiahui Fan; Huaping Li; Xiang Nie; Zhongwei Yin; Yanru Zhao; Chen Chen; Dao Wen Wang

doi:10.18632/oncotarget.14561

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Research Papers:

MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN

Jiahui Fan, Huaping Li, Xiang Nie, Zhongwei Yin, Yanru Zhao, Chen Chen and Dao Wen Wang _

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Oncotarget. 2017; 8:13450-13463. https://doi.org/10.18632/oncotarget.14561

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Abstract

Jiahui Fan1, Huaping Li1, Xiang Nie1, Zhongwei Yin1, Yanru Zhao1, Chen Chen1, Dao Wen Wang1

1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Correspondence to:

Chen Chen, email: [email protected]

Dao Wen Wang, email: [email protected]

Keywords: miR-30c-5p, NAFLD, hepatic steatosis, FASN, db/db

Received: November 11, 2016 Accepted: January 02, 2017 Published: January 09, 2017

ABSTRACT

Approximately 15–40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis. Moreover, down-regulation of FASN by siRNA attenuated some key features of NAFLD, including decreased triglyceride accumulate and lipid deposition. Our findings reveal a new role of miR-30c-5p in counterbalancing fatty acid biosynthesis, which is sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice.

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Research Papers:

MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN

Abstract