6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 Cascade

• DOI: 10.1016/j.jcmgh.2021.06.007
• Publication Date: 2021-06-15T23:07:20Z
• Authors: Jiyun Ahn; Hyunjung Lee; Chang Hwa Jung; Seung Yeon Ha; Hyo-Deok Seo; Young In Kim; Taeyoul Ha
• Keywords: Steatosis; Hepatocyte nuclear factors; Lipid droplet

Background & AimsThe development of nonalcoholic fatty liver disease (NAFLD) can be modulated by microRNAs (miRNA). Dietary polyphenols modulate the expression miRNA such as miR-467b-3p in liver. In addition, 6-gingerol (6-G), functional polyphenol ginger, has been reported to ameliorate hepatic steatosis; however, exact mechanism involved and role remain elusive. this study, we assessed pathogenesis steatosis regulation 6-G through hepatocyte nuclear factor 4α (HNF4α).MethodsmiR-467b-3p was measured free acid (FFA)-treated hepatocytes or from high-fat diet (HFD)-fed mice. Gain- loss-of-function induced using miR-467b-3p–specific mimic inhibitor, respectively. exposed FFA-treated cells HFD-fed The HNF4α/miR-467b-3p/GPAT1 axis mouse human tissues.ResultsWe found that down-regulated tissues mice Hepa1-6 cells. Overexpression decreased intracellular lipid accumulation mitigated via negative glycerol-3-phosphate acyltransferase-1 (GPAT1). up-regulation observed. inhibited FFA-induced steatosis. Moreover, it increased transcriptional activity HNF4α, resulting increase subsequent decrease GPAT1. signaling also observed samples with steatosis.ConclusionsOur findings establish a novel which improves NAFLD. This suggests targeting cascade may used potential therapeutic strategy control (HNF4α). tissues. We Our