Ablation of DJ-1 impairs brown fat function in diet-induced obese mice

Abstract

This study was conducted to investigate the effects of DJ-1 deficiency on brown adipose tissue (BAT) function in mice. DJ-1 knockout (KO) mouse models and wild-type littermates placed on a normal diet or high-fat diet were utilized to demonstrate the direct consequences of DJ-1 deletion on BAT characteristics, thermogenic ability, lipid metabolism, and microenvironment regulation. Global DJ-1 KO mice had defective brown adipose tissue activity culminating in a profound whitening of BAT. Despite aberrations in inactive BAT associated with greater lipid accretion, decreased sympathetic activity, mitochondrial dysfunction, reduced vascularity, and autophagy activation, we found that the body weight and energy balance were unaffected in male mice depleted of DJ-1. Taken together, the results of this study suggest that male DJ-1 KO mice exhibit defects in BAT activity but do not gain more weight, revealing that BAT activity is not necessarily required for predisposing DJ-1 KO mice to obesity. Therefore, therapeutic targeting of DJ-1 in BAT could provide novel insights into the treatment of obesity.

Keywords: Autophagy; Brown adipose tissue; DJ-1; Mitochondria; Obesity; Whitening.