Bromide alleviates fatty acid-induced lipid accumulation in mouse primary hepatocytes through the activation of PPARα signals.

Increased plasma free fatty acids (FFAs) and liver triglyceride (TG) accumulations have been implicated in the pathogenesis of hepatic steatosis. On the other hand, trace elements function as essential cofactors that are involved in various biochemical processes in mammals, including metabolic homeostasis. Notably, clinical and animal studies suggest that the plasma levels of bromide negatively correlate with those of TG, total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C). However, the effect of bromide on lipid accumulation and the direct molecular target responsible for its action remains unknown. Oil red O (ORO) and Nile red staining were used to detect the effect of bromide on lipid accumulation in mouse primary hepatocytes (PHs) treated with different doses of sodium bromide (NaBr) in the presence of FFAs (0.4 mM oleate/palmitic acid 1:1). Spectrophotometric and fluorometric analyses were performed to assess cellular TG concentrations and rates of fatty acid oxidation (FAO), respectively, in mouse PHs. We found that bromide decreased FFA-induced lipid accumulation and increased FFA-inhibited oxygen consumptions in mouse PHs in a dose-dependent manner via activation of PPARα. Mechanical studies demonstrated that bromide decreased the phosphorylation levels of JNK. More importantly, the PPARα-specific inhibitor GW6471 partially abolished the beneficial effects of bromide on mouse PHs. Bromide alleviates FFA-induced excessive lipid storage and increases rates of FAO through the activation of PPARα/JNK signals in mouse PHs. Therefore, bromide may serve as a novel drug in the treatment of hepatic steatosis.