Research Perspective|Volume 2, Issue 8|pp 527—534

Controlling SIRT1 expression by microRNAs in health and metabolic disease

Jiyoung Lee¹, Jongsook Kim Kemper

¹Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign, IL 61801, USA

Received: July 30, 2010Accepted: August 4, 2010Published: August 5, 2010

Copyright: © 2010 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

SIRT1 is a NAD^+-dependent deacetylase implicated in longevity and diverse physiological processes. SIRT1, as a key mediator of beneficial effects of caloric restriction, regulates lipid and glucose metabolism by deacetylating metabolic regulators, as well as histones, in response to nutritional deprivation. Here we discuss how SIRT1 levels are regulated by microRNAs (miRs) which are emerging as important metabolic regulators; the recently identified nuclear receptor FXR/SHP cascade pathway that controls the expression of miR-34a and its target SIRT1; and a FXR/SIRT1 positive feedback regulatory loop, which is deregulated in metabolic disease states. The FXR/miR-34a pathway and other miRs controlling SIRT1 may be useful therapeutic targets for age-related diseases, including metabolic disorders.