Epigenetic regulation: evaluation of miRNAs as potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD) diet-induced obese mice treated with Camelia sinensis

• Grant number: 15/21785-1
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2016
• Effective date (End): December 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosemari Otton
• Grantee: Letícia Torres Ferreira
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

The alarming growth of obesity has become a world challenge to public health. The epidemic proportions of obesity prevalence stimulated scientific interest in the etiology and the search for therapeutic interventions capable of preventing the co-morbidities associated with it. The non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of progressive liver dysfunction that is closely related to obesity, diabetes and insulin resistance. Accordingly, many researchers look to find bioactive compounds derived from medicinal plants capable of treating and preventing the development of hepatic steatosis or its progression to non-alcoholic steatohepatitis. Among them, the Camellia sinensis plant, which is obtained green tea, widely consumed in different parts of the world. The polyphenol content of this plant gives many beneficial effects on health. However, the molecular mechanisms behind these effects of green tea remain unknown. Recently it became clear that polyphenols can interact with signaling pathways, modulating the activity of transcription factors and thus the expression of genes, suggesting that these cellular and molecular targets represent the underlying mechanism of action of the beneficial effects of polyphenols. Recent studies have demonstrated the ability to post-transcriptional gene regulation of polyphenols via modulation of the expression of microRNAs (miRNAs). Polyphenols are able to regulate expression of a variety of processes associated miRNAs involved in the pathogenesis of NAFLD. This project is linked to FAPESP project number 2013 / 22293-0, which aims to identify specific miRNAs profiles in the liver of obese mice supplemented with green tea extract using miRNA qPCR array technology. In this project we aim to evaluate the specific expression of miRNAs associated with NAFLD in obese animals and obese liver treated with green tea from data obtained with the miRNA qPCR array. We intend to identify three most altered miRNAs and correlate them with NAFLD identifying target genes of these miRNAs, validating the genes in vivo experiments and evaluating the major pathways modulated by miRNAs through gene and protein expression. Thus the various beneficial health effects from the regular consumption of green tea have found, together with such assessments can open new perspectives in the treatment of obesity and NAFLD through epigenetic regulation, and miRNAs as potential targets of its mechanism of action. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, LETICIA TORRES; BATISTA DE SOUSA FILHO, CELSO PEREIRA; MARINOVIC, MARCELO PARADISO; RODRIGUES, ALICE CRISTINA; OTTON, ROSEMARI. Green tea polyphenols positively impact hepatic metabolism of adiponectin-knockout lean mice. Journal of Functional Foods, v. 64, JAN 2020. (16/12059-8, 15/24789-8, 15/21785-1)

TORRES, L. F.; COGLIATI, B.; OTTON, R.. Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2019, DEC 4 2019. (13/22293-0, 15/21785-1)