6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade
- Authors
- Ahn, Jiyun; Lee, Hyunjung; Jung, Chang Hwa; Ha, Seung Yeon; Seo, Hyo-Deok; Kim, Young In; Ha, Taeyoul
- Issue Date
- Jan-2021
- Publisher
- ELSEVIER INC
- Keywords
- 6-gingerol; GPAT1; HNF4α; MicroRNA; NAFLD
- Citation
- Cellular and Molecular Gastroenterology and Hepatology, v.12, no.4, pp.1201 - 1213
- Journal Title
- Cellular and Molecular Gastroenterology and Hepatology
- Volume
- 12
- Number
- 4
- Start Page
- 1201
- End Page
- 1213
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82602
- DOI
- 10.1016/j.jcmgh.2021.06.007
- ISSN
- 2352-345X
- Abstract
- Background & Aims: The development of nonalcoholic fatty liver disease (NAFLD) can be modulated by microRNAs (miRNA). Dietary polyphenols modulate the expression of miRNA such as miR-467b-3p in the liver. In addition, 6-gingerol (6-G), the functional polyphenol of ginger, has been reported to ameliorate hepatic steatosis; however, the exact mechanism involved and the role of miRNA remain elusive. In this study, we assessed the role of miR-467b-3p in the pathogenesis of hepatic steatosis and the regulation of miR-467b-3p by 6-G through the hepatocyte nuclear factor 4α (HNF4α). Methods: miR-467b-3p expression was measured in free fatty acid (FFA)-treated hepatocytes or liver from high-fat diet (HFD)-fed mice. Gain- or loss-of-function of miR-467b-3p was induced using miR-467b-3p–specific miRNA mimic or miRNA inhibitor, respectively. 6-G was exposed to FFA-treated cells and HFD-fed mice. The HNF4α/miR-467b-3p/GPAT1 axis was measured in mouse and human fatty liver tissues. Results: We found that miR-467b-3p was down-regulated in liver tissues from HFD-fed mice and in FFA-treated Hepa1-6 cells. Overexpression of miR-467b-3p decreased intracellular lipid accumulation in FFA-treated hepatocytes and mitigated hepatic steatosis in HFD-fed mice via negative regulation of glycerol-3-phosphate acyltransferase-1 (GPAT1). In addition, miR-467b-3p up-regulation by 6-G was observed. 6-G inhibited FFA-induced lipid accumulation and mitigated hepatic steatosis. Moreover, it increased the transcriptional activity of HNF4α, resulting in the increase of miR-467b-3p and subsequent decrease of GPAT1. HNF4α/miR-467b-3p/GPAT1 signaling also was observed in human samples with hepatic steatosis. Conclusions: Our findings establish a novel mechanism by which 6-G improves NAFLD. This suggests that targeting of the HNF4α/miR-467b-3p/GPAT1 cascade may be used as a potential therapeutic strategy to control NAFLD. © 2021 The Authors
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