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Research Paper|Volume 12, Issue 21|pp 22019—22045

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease

Jiabing Zhan1,2, Huizhen Lv3,4, Beibei Dai1,2, Shuai Yuan1,2, Jiahui Fan1,2, Yanru Zhao1,2, Zhongwei Yin1,2, Dao Wen Wang1,2, Chen Chen1,2, Huaping Li1,2
  • 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
  • 3State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
  • 4Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin Key Laboratory of Metabolic Diseases, Tianjin, China
* Equal contribution
Received: December 24, 2019Accepted: July 30, 2020Published: November 7, 2020
https://doi.org/10.18632/aging.104040

Copyright: © 2020 Zhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Multiple metabolic disorders, such as hyperlipidemia, hyperglycemia, insulin resistance and obesity, have been reportedly associated with NAFLD, but little is known about the detailed mechanisms.

Methods and Results: Here, we explored the effects of multiple metabolic disorders, especially hyperglycemia on lipid accumulation in liver using several well-established animal models. We found that liver lipid deposition was increased in both type 1 diabetes and high-fat diet (HFD) induced hyperlipidemia models, suggesting that either hyperglycemia or hyperlipidemia alone or together was able to trigger NAFLD. Moreover, we tested whether miR-320, a miRNA promoting lipid accumulation in heart revealed by our previous study, also participated in NAFLD. Though miR-320 treatment further increased liver lipid deposition in type 1 diabetes and HFD-feeding mice, it showed no effect in leptin-receptor deficient db/db mice. Interestingly, miR-320 affected different target genes in cytosol and nucleus, respectively, which collectively led to liver lipid overload.

Conclusions: Our findings illustrated the complex roles of miRNAs in subcellular fractions including nucleus and cytoplasm, which may lead to new insights into the mechanisms and treatment strategies for NAFLD in the future.