MicroRNAs on adiponectin signalling: potential therapeutical targets of insulin resistance and insulin resistance linked diseases.

Abstract

Adiponectin is an adipokine produced and secreted, mainly by adipose tissue that has antidiabetic and antiatherogenic properties. Low levels of adiponectin are found in obesity and diabetis subjects. Adiponectin receptors, AdipoR1 and AdipoR2 are the major receptors for adiponectin, and they are key regulators of glucose and lipid metabolism. Adipor1/r2 double knockout mice abrogate adiponectin-binding and glucose-lowering effects of adiponectin, and result in high liver triglycerides content, insulin resistance and glucose intolerance. Both hipoadiponectinemia and low expression levels of AdipoR1 and R2 are associated to obesity and obesity-linked diseases such as diabetes mellitus type 2 and non-alcoholic fatty liver disease (NAFLD). Therefore, therapeutic interventions resulting in higher production of adiponectin and/or higher expression of AdipoRs may be important options to prevent obesity-linked diseases. Recently, post-transcriptionally regulation of Adiponectin (Adipoq) and Adipor1/r2 genes by microRNAs has been shown in obese humans and experimental obesity mice models. As well as this, many studies have demonstrated that a dysregulation of microRNAs expression may lead to insulin resistance and such studies have pointed circulating microRNAs as biomarkers of the progress of diabetes type 2 and NAFLD. Thu, the aim of our study is to find differentially expressed microRNAs in liver and skeletal muscle of DIO mice associated to adiponectin binding of Adipor1/r2 and serve as potential therapeutical targets to restore insulin resistance, and consequently treat or prevent diabetes type 2 and NAFLD. (AU)