Chronic Fatty Acid Depletion Induces Uncoupling Protein 1 (UCP1) Expression to Coordinate Mitochondrial Inducible Proton Leak in a Human-Brown-Adipocyte Model.
Chronic Fatty Acid Depletion Induces Uncoupling Protein 1 (UCP1) Expression to Coordinate Mitochondrial Inducible Proton Leak in a Human-Brown-Adipocyte Model.
复制标题
慢性脂肪酸消耗诱导解偶联蛋白1 （UCP1）表达协调线粒体诱导的质子泄漏在人类棕色脂肪细胞模型中。
作者：
产热棕色脂肪有助于成年人的代谢健康。众所周知，肥胖会抑制脂肪组织的布朗宁及其活性。在此，我们发现，慢性脂肪酸（FA）消耗诱导解偶联蛋白1（UCP1）的化学化合物诱导的棕色脂肪细胞（ciBA）的表达。在无FA条件下从人皮肤成纤维细胞转化的ciBA具有低细胞内甘油三酯水平和强烈激活的UCP1表达。长期治疗与肉毒碱也减少甘油三酯的积累和诱导UCP1的表达。转录组分析表明，UCP1诱导伴随着脂质代谢基因的激活。FA耗尽的条件下抑制线粒体质子泄漏活性和线粒体膜电位（MMP），尽管保持高UCP1表达。有证据表明，UCP1表达被诱导以补偿低MMP下的质子泄漏活性。我们的研究报告了在不同营养条件下，人棕色脂肪细胞中UCP1表达和能量状态的调节机制。
Thermogenic brown fat contributes to metabolic health in adult humans. Obese conditions are known to repress adipose-tissue browning and its activity. Herein, we found that chronic fatty acid (FA) depletion induced uncoupling protein 1 (UCP1) expression in the chemical-compound-induced brown adipocytes (ciBAs). The ciBAs, converted from human dermal fibroblasts under FA-free conditions, had low intracellular triglyceride levels and strongly activated UCP1 expression. Prolonged treatment with carnitine also reduced triglyceride accumulation and induced UCP1 expression. Transcriptome analysis revealed that the UCP1 induction was accompanied by the activation of lipid metabolic genes. The FA-depleted conditions repressed mitochondrial proton-leak activity and mitochondrial membrane potential (MMP), despite maintaining a high UCP1 expression. The evidence suggested that UCP1 expression was induced to compensate for the proton-leak activity under low MMP. Our study reports a regulatory mechanism underlying UCP1 expression and mitochondrial-energy status in human brown adipocytes under different nutritional conditions.