Does microRNA Perturbation Control the Mechanisms Linking Obesity and Diabetes? Implications for Cardiovascular Risk

Abstract

Metabolic disorders such as obesity and type 2 diabetes (T2D) are considered the major risk factors for the development of cardiovascular diseases (CVD). Although the pathological mechanisms underlying the mutual development of obesity and T2D are difficult to define, a better understanding of the molecular aspects is of utmost importance to identify novel therapeutic targets. Recently, a class of non-coding RNAs, called microRNAs (miRNAs), are emerging as key modulators of metabolic abnormalities. There is increasing evidence supporting the role of intra- and extracellular miRNAs as determinants of the crosstalk between adipose tissues, liver, skeletal muscle and other organs, triggering the paracrine communication among different tissues. miRNAs may be considered as risk factors for CVD due to their correlation with cardiovascular events, and in particular, may be related to the most prominent risk factors. In this review, we describe the associations observed between miRNAs expression levels and the most common cardiovascular risk factors. Furthermore, we sought to depict the molecular aspect of the interplay between obesity and diabetes, investigating the role of microRNAs in the interorgan crosstalk. Finally, we discussed the fascinating hypothesis of the loss of protective factors, such as antioxidant defense systems regulated by such miRNAs.

Keywords: CVD; T2D; atherosclerosis; cardiovascular complications; diabetes; inflammation; metabolic syndrome; microRNA; obesity.

Figure 1

Schematic depiction of exo-miRs released by surrounding organs. Adipose tissue (AT) acts as an active endocrine and energy-supply organ. It has emerged as a source of extracellular microRNAs (miRNAs), exerting a paracrine communication between the liver, skeletal muscle, pancreas and cardiovascular system. The strong connection among organs may be attractive targets for novel therapeutic strategies.