Abstract 16501: Genetic Deletion and Pharmacological Inhibition of MiR-92a Reduce Obesity

Obesity and type 2 diabetes are key risk factors for coronary artery diseases. MicroRNAs (miRs) are small non-coding RNAs, which act as negative regulators of gene expression and have been shown to modulate cardiovascular diseases and control energy homeostasis. Inhibition of miR-92a improved neovascularization and endothelial cell (EC) function. To determine the metabolic role of miR-92a, we analyzed genetic and pharmacological miR-92a depletion on obesity. MiR-92a-/- mice are resistant to high-fat diet (HFD) induced obesity (weight gain from 6-14.5 weeks of age: -24±4% vs. WT; p<0.01). The percentage of total body fat (dual energy X-ray absorptiometry: -20±6%; p=0.04), weight of epididymal white adipose tissue (WAT) (-54±9%; p=0.04), and consistently, white adipocytes size (-24±7%; p=0.03) were reduced in miR-92a-/- mice. Additionally, miR-92a-/- mice exhibit decreased levels of cholesterol (-27±6%; p<0.01) and triglyceride (-25±4%; p=0.02) as well as improved glucose tolerance (-21±6%; p=0.04). Next, t...