Bile acid signaling activates MiR-26a to regulate insulin sensitivity and metabolism of glucose and lipids
2nd International Conference on Hepatology
May 09-11, 2016 Chicago, USA

Wendong Huang

City of Hope Diabetes and Metabolism Research Institute, USA

Posters & Accepted Abstracts: J Liver

Abstract:

Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. GPBAR1/TGR5 is a G protein�??coupled receptor of bile acids. TGR5 is known to regulate the BA homeostasis and energy metabolism. Recent studies highlight an important role of TGR5 in alleviating obesity and improving glucose regulation, however, the mechanism of which is still unclear. Here we report that TGR5 is involved in mediating the anti-obesity and anti-hyperglycemia effect of a natural compound, oleanolic acid. By comparing the miRNA profiles between wild type and TGR5-/- livers after OA treatment, we identified miR-26a as a novel downstream target gene of TGR5 activation. MicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in human diseases, including T2D. MiR-26a plays critical roles in tumorigenesis, however its function in cellular metabolism remains unknown. Here we identify miR-26a as a novel regulator for insulin signaling and metabolism of glucose and lipids. Expression of miR-26a in the liver is decreased in two obese mouse models and in overweight humans. Global or liver-specific overexpression of miR-26a in mice improves insulin sensitivity, decreases hepatic glucose production, and decreases fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in mice impairs insulin sensitivity, enhances glucose production, and increases fatty acid synthesis. Mechanistically, miR-26a targets several key regulators of hepatic metabolism and insulin signaling. These findings reveal a novel role of miR-26a in regulating liver metabolism, and provide a potential target for the treatment of T2D.

Biography :

Email: whuang@coh.org