MicroRNAs as metabolic mediators in the communication among white adipose tissue, liver and skeletal muscle in obese mice

Abstract

Obesity is associated with a chronic low-grade inflammation and, for this reason, is considerated one of the major risk factors for developing insulin resistance. Recently, microRNAs in adipose tissue was proposed to be secreted into plasma through microvesicles and then transferred to other cell types, playing an important role in intercellular communication. Thus, we believe that Obesity and insulin resistance may cause alterations in the tissue expression pattern and release of circulating microRNAs from the main tissues involved with energy metabolism (liver, muscle and white adipose tissue). The overall objective of this project is to investigate important microRNAs for the mechanisms of communication between liver, skeletal muscle and white adipose tissue in Obesity and its major metabolic implications. For this, in vivo and in vitro models will be used. Male C57BL/6 mice will receive control or high fat diet supplemented with condensed milk for twelve weeks. After this period, the insulin sensitivity, glucose tolerance, and plasma biochemical parameters will be evaluated and the quantitative expression of microRNAs and its target genes of white adipose tissue, gastrocnemius muscle, liver and plasma will be perform. Serum isolated exosomes of obese mice will be injected in control mice followed by subsequent analysis of metabolic and molecular parameters. The primary culture of adipocytes, myoblasts and hepatocytes will be performed with the purpose of confirming the communication, through exosomal microRNA, between the different tissues. With this study, we expect a greater understanding of the mechanisms of communication between different tissues via microRNAs and their correlation with Obesity and insulin resistance. (AU)