Bromide alleviates fatty acid-induced lipid accumulation in mouse primary hepatocytes through the activation of PPAR alpha signals
Bromide alleviates fatty acid-induced lipid accumulation in mouse primary hepatocytes through the activation of PPAR alpha signals
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溴化物通过激活 PPAR α 信号减轻脂肪酸诱导的小鼠原代肝细胞脂质积累
DOI：
10.1111/jcmm.14347
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发表时间：
2019
影响因子：
5.3
通讯作者：
Chen Siyu
中科院分区：
文献类型：
--
作者：
Shi Yujie;Zhang Wenxiang;Cheng Yinlong;Liu Chang;Chen Siyu
血浆游离脂肪酸(FFAs)和肝脏甘油三酯(TG)蓄积增加与肝脏脂肪变性的发病机制有关。另一方面，微量元素作为重要的辅因子参与哺乳动物的各种生化过程，包括代谢动态平衡。值得注意的是，临床和动物研究表明，血浆溴化物水平与甘油三酯、总胆固醇(TC)和高密度脂蛋白胆固醇(HDLC)呈负相关。然而，溴化物对脂质积累的影响以及负责其作用的直接分子靶点仍不清楚。采用油红O(ORO)和尼罗红(Nile Red)染色方法，观察了不同剂量的溴化钠(NaBR)与游离脂肪酸(FFAs)(0.4 mM油酸/棕榈酸)共同作用时，溴化物对小鼠原代肝细胞(PHS)脂质蓄积的影响。用分光光度法和荧光法分别测定小鼠PHS细胞内甘油三酯浓度和脂肪酸氧化速率。我们发现，溴化物通过激活PPARα，以剂量依赖的方式减少了游离脂肪酸诱导的小鼠PHS的脂质积聚，增加了FFA抑制的氧耗量。力学研究表明，溴化物降低了JNK的磷酸化水平。更重要的是，PPARα特异性抑制剂GW6471部分取消了溴对小鼠PHS的有利作用。溴化物通过激活PPARα/JNK信号，减轻游离脂肪酸诱导的过量脂肪储存，增加粮农组织的比率。因此，溴化物可能成为治疗肝脏脂肪变性的一种新药。
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 ofPPARα. Mechanical studies demonstrated that bromide decreased the phosphorylation levels of JNK. More importantly, thePPARα‐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 ofPPARα/JNK signals in mouse PHs. Therefore, bromide may serve as a novel drug in the treatment of hepatic steatosis.