Poster abstracts
Poster number 108 submitted by Takahisa Nakamura
Role of hepatic RNA silencing in the pathogenesis of obesity
Takahisa Nakamura (Pediatric Endocrinology, Cincinnati Childrens Hospital )
Abstract:
The worldwide prevalence of obesity has reached pandemic proportions, and with it have come other associated metabolic diseases. Despite the urgent need for treatment, the pathogenic mechanisms underlying this cluster of metabolic disease are still unclear, and effective preventive and/or therapeutic strategies are limited. Recent studies have revealed significant roles for microRNA (miRNA)-mediated events in the development and progression of metabolic diseases. For instance, the global dysregulation of miRNA biogenesis is triggered in an obese condition, of which specific miRNAs could drive pathophysiological changes and disrupt energy metabolism. However, a fundamental question if obesity evokes functional changes in miRNA-regulatory machinery, resulting in the abnormal biogenesis of miRNAs participating in the pathogenesis of obesity and metabolic disturbance, has not yet been addressed, despite drastic changes in global miRNA expression profile in the obese condition. We have recently discovered novel roles of hepatic miRNA-regulatory machinery in the pathogenesis of obesity and regulation of systemic energy homeostasis. These components in the liver regulate glucose- and fatty acids-driven energy production via RNA silencing of genes critical for mitochondrial functions and affect systemic energy homeostasis. These results have significant implications for understanding the role of hepatic miRNA and its regulatory machinery in the regulation of metabolic homeostasis and for defining an entirely novel class of therapeutics for metabolic diseases.
References:
Cai Zhang et al., "Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to
AMPK activation and obesity-associated pathophysiology" Nature Communications (In press)
Keywords: Obesity , RNA silencing, Argonaute 2