Molecular Basis of Obesity and Obesity-induced Metabolic Diseases

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

The current obesity epidemic in the US is the major contributor to the soaring rates of metabolic diseases and to skyrocketing health care costs. Yet the molecular and pathological mechanisms by which obesity induces metabolic disorders remain incompletely understood, and therapeutic interventions for obesity and related metabolic abnormalities are limited. In recent years, tens of thousands of long non-coding RNAs lncRNAs (lncRNAs) have been identified to constitute a significant portion of the human genome and play a diverse role in biological processes. To systemically analyze the role of lncRNAs in human disease, we have identified liver-enriched human lncRNAs that exhibit altered expression in patients with metabolic disorders. We also confirmed the in vivo role of several liver-enriched lncRNAs in lipid metabolism by performing gain- and/or loss-of-function analyses of the lncRNAs in regular mouse models or a humanized mouse model in which the liver is populated with human hepatocytes. Intriguingly, we found that short motifs on these lncRNAs could serve as drug targets or even therapeutic agents themselves for metabolic diseases. Our work collectively supports that human lncRNAs can function as critical metabolic regulators and may play a role in the pathogenesis of metabolic diseases.