Identification and validation of miRNA target genes in adipose tissue and liver of obese mice in response to treatment with green tea extract

Abstract

Obesity is a growing public health problem worldwide. Its high prevalence in the population awakens the scientific interest in the etiology and the search for therapeutic interventions that promote the loss of fat mass to preventing co-morbidities such as diabetes and cardiovascular and neurological diseases. In this regard, many researchers are trying to find bioactive compounds derived from medicinal plants capable of treating and preventing obesity. Among them, the plant Camellia sinensis, known by the common names green tea, black tea, oolong or white tea is widely consumed in different parts of the world. Catechins, the polyphenolic compounds more abundant in this plant, have many beneficial health effects including effects on the redox state, inflammation, glucose and lipid metabolism, cell proliferation and hypertension, which are associated with the pathophysiology of obesity. However, the molecular mechanisms behind the effects of green tea extract are still unknown. Thus, we intent to realize a comprehensive approach to study molecular mechanisms of gene regulation in adipose tissue and liver of obese mice undergoing treatment with green tea extract. We will focus mainly on post transcriptional control provided by small non-coding RNAs, especially microRNAs, which play an important role in the pathogenesis of obesity and its comorbidities. Thus, evaluating microRNAs modulated with chronic supplementation with green tea extract on obese animals may elucidate new molecular mechanisms of their beneficial effects, and promotes the opportunity to identify new microRNAs associated with the pathophysiology of obesity. The experimental approach is exploratory at first, where through analyses of small RNAs by microarray technology we will identify microRNAs differentially expressed among groups, especially those modulated by treatment with green tea. In the second stage of this project, we will select some microRNAs to validate the biological relevance of in vitro techniques through loss or gain of their function. This robust experimental design will be important to broaden the knowledge about the role of green tea in obesity and identify new therapeutic approaches. (AU)