Abstract
Background/Aims Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. It is currently the most common chronic liver disease with complex pathogenesis and challenging treatment. Here, we investigated the hepatoprotective role of green tea (GT) and determined the involvement of miRNAs and its mechanism of action. Methods Male C57Bl/6 mice were fed with a high-fat diet for 4 weeks. After this period, the animals received gavage with GT (500 mg/kg body weight) over 12 weeks (5 days/week). HepG2 cell lines were transfected with miR-34a or miR-194 mimetics and inhibitors to validate the in vivo results or were treated with TNF-α to evaluate miRNA regulation. Results GT supplementation protects against NAFLD development by altering lipid metabolism, increasing gene expression involved in triglycerides and fatty acid catabolism, and decreasing uptake and lipid accumulation. This phenotype was accompanied by miR-34a downregulation and an increase in their mRNA targets Sirt1, Pparα, and Insig2. GT upregulated hepatic miR-194 by inhibiting TNF-α action leading to a decrease in miR-194 target genes Hmgcs/Apoa5. Conclusion Our study identified for the first time that the beneficial effects of GT in the liver can be due to the modulation of miRNAs, opening new perspectives for the treatment of NAFLD focusing on epigenetic regulation of miR-34a and miR-194 as green tea targets.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in Western countries, affecting about 30% of the worldwide population [1,2,3]
We demonstrate that the green tea (GT) supplementation protects against obesity and NAFLD development in high-fat diet (HFD)-fed mice by altering lipid metabolism, increasing genes involved in TG catabolism and fatty acid oxidation, and decreasing lipid uptake and accumulation as well as cholesterol synthesis
We have some evidence that the underlying mechanism by which the GT alters hepatic metabolism could involve epigenetic regulation of miR-34a and miR-194 that control the expression of target genes such as Sirt1/Ppara/Insig2 and Hmgcs2/Apoa5, respectively
Summary
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in Western countries, affecting about 30% of the worldwide population [1,2,3]. The mechanisms underlying the development and progression of NAFLD are displayed in a multiple hit model that involves insulin resistance (IR), nutritional factors overload, gut microbiota dysfunction, endoplasmic reticulum (ER) stress, inflammatory liver environment (cytokine release), and genetic and epigenetic factors [5,6,7]. Among the main biological effects attributed to GT polyphenols, we can highlight the antioxidant, anti-inflammatory, antitumor, antidiabetic, antiobesity, and hepatoprotective activities [8, 9]. Several studies have related the GT consumption to the improvement and prevention of NAFLD [10,11,12,13]. The administration of EGCG, the main polyphenol in GT, improves liver function and morphology, as well as reducing body weight and ameliorates insulin sensitivity [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
