Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism.

Tooru Mizuno

doi:10.3390/nu10111600

Abstract

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

Highlights

Genetic factors contribute to the susceptibility to metabolic diseases
A genome-wide association study has identified common variants in the fat mass and obesity associated (FTO) gene to be associated with obesity and type 2 diabetes [1,2,3]
These findings suggest that FTO is implicated in the regulation of both body weight and glucose metabolism

Summary

Introduction

Genetic factors contribute to the susceptibility to metabolic diseases. A genome-wide association study has identified common variants in the fat mass and obesity associated (FTO) gene to be associated with obesity and type 2 diabetes [1,2,3]. Subsequent studies demonstrated that FTO variants are associated with an increased risk of type 2 diabetes at least partly independent of obesity [4,6,7,8,9,10,11,12]. These findings suggest that FTO is implicated in the regulation of both body weight and glucose metabolism. It is proposed that FTO plays a role in the regulation of metabolism, possibly by altering gene expression in metabolically active tissues

Biological Function of FTO

Regulation of Hepatic FTO Expression by Metabolic Signals

Hepatic FTO Expression in Obesity and Diabetes

Hepatic FTO and Glucose Metabolism

Hepatic FTO and Lipid Metabolism

Future Perspectives