Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model

Autor(es)

Torres, L. F. ^[1] ; Cogliati, B. ^[2] ; Otton, R. ^[1]

Afiliação do(s) autor(es)

^[1] Cruzeiro do Sul Univ, Interdisciplinary Postgrad Programme Hlth Sci, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2019, DEC 4 2019.
• Citações Web of Science: 0

Resumo

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-alpha 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, Ppar alpha, and Insig2. GT upregulated hepatic miR-194 by inhibiting TNF-alpha 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. (AU)

• Processo FAPESP: 13/22293-0 - Identificação de miRNAs e validação de genes-alvo no tecido adiposo e fígado de camundongos obesos em resposta ao tratamento com extrato de chá verde
• Beneficiário: Rosemari Otton
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/21785-1 - Regulação epigenética: avaliação de miRNAs como potenciais alvos terapêuticos na doença hepática gordurosa não alcoólica (DHGNA) em camundongos obesos tratados com Camellia sinensis
• Beneficiário: Letícia Torres Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado