Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

Yaqin Chen,Rong Xiang,Shuiping Zhao,Zhihong Wu

doi:10.1038/srep27486

Abstract

Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

Highlights

Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues
The expression levels of resistin and TNF-αwere markedly elevated after 14 weeks of feeding (Fig. 1d). These findings provide evidence of chronic inflammation occurring in obese adipose tissue
Our findings suggested that Endoplasmic reticulum (ER) stress, chronic inflammation and metabolic disorders occur in adipose tissue of obese mice

Summary

Introduction

Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. Chemical or pharmaceutical chaperones, such as 4-phenyl butyric acid (4-PBA), ursodeoxycholic acid and its taurine-conjugated derivative (TUDCA), are a group of low molecular weight compounds known to stabilize protein conformation in the ER, and facilitate the trafficking of mutant proteins[10]. It can repress ER stress/UPR activation in vitro and in vivo[11,12]. NF-κB plays an important role in adipocytes inflammation in human and experimental models of metabolic www.nature.com/scientificreports/

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