6-Gingerol Ameliorates Hepatic Steatosis via HNF4α/miR-467b-3p/GPAT1 CascadeSummary
| Autor: | Chang Hwa Jung, Hyunjung Lee, Hyo-Deok Seo, Jiyun Ahn, Young In Kim, Tae-Youl Ha, Seung Yeon Ha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male HFD high-fat diet Catechols Gene Expression ACC acetyl-CoA carboxylase RC799-869 Pathogenesis Mice 0302 clinical medicine Genes Reporter Non-alcoholic Fatty Liver Disease Nonalcoholic fatty liver disease miRNA microRNA Original Research chemistry.chemical_classification Chemistry Fatty liver Gastroenterology MicroRNA 1-Acylglycerol-3-Phosphate O-Acyltransferase Diseases of the digestive system. Gastroenterology mRNA messenger RNA ChIP chromatin immunoprecipitation Hepatocyte nuclear factors HF high-fat diet–fed group UTR untranslated region Hepatocyte Nuclear Factor 4 030211 gastroenterology & hepatology RNA Interference Fatty Alcohols Intracellular medicine.medical_specialty TAG triacylglycerol DNL de novo lipogenesis HNF4α hepatocyte nuclear factor 4α 6-G 6-gingerol GPAT1 03 medical and health sciences Structure-Activity Relationship cDNA complementary DNA GPAT glycerol-3-phosphate acyltransferase Internal medicine NAFLD microRNA FFA free fatty acid medicine Animals Humans HNF4α Hepatology DARTS drug-affinity–responsive target stability TLDA TaqMan low-density arrays Fatty acid medicine.disease Lipid Metabolism Disease Models Animal MicroRNAs 030104 developmental biology Endocrinology Gene Expression Regulation LysoPA lysophosphatidic acid NAFLD nonalcoholic fatty liver disease Steatosis 6-gingerol |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 4, Pp 1201-1213 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
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