A lack of ChREBP inhibits mitochondrial cristae formation in brown adipose tissue
A lack of ChREBP inhibits mitochondrial cristae formation in brown adipose tissue
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DOI：
10.1007/s11010-021-04178-2
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发表时间：
2021-05-21
影响因子：
4.3
通讯作者：
Suzuki, Keiichiro
中科院分区：
文献类型：
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作者：
Sakiyama, Haruhiko;Li, Lan;Suzuki, Keiichiro
碳水化合物反应元件结合蛋白（ChREBP）是一种葡萄糖反应性转录因子，可增加多个基因的转录。ChREBP高度定位于肝脏中，在那里它上调编码糖酵解和脂肪生成酶的基因的表达，导致过量的碳水化合物转化为储存脂肪。ChREBP敲除（KO）小鼠显示抗肥胖表型。然而，在这个时候，ChREBP在脂肪组织中的作用仍然不清楚。因此，检查了ChREBP KO小鼠线粒体棕色脂肪组织（BAT）的能量代谢和形态。我们发现电子传递系统蛋白的表达水平增加，包括线粒体解偶联蛋白（UCP1），以及线粒体结构改变，如嵴发育不良和ChREBP KO小鼠BAT中存在小线粒体。质谱分析显示，脂肪酸合酶在ChREBP KO小鼠的BAT中不存在，这可能导致脂肪酸和心磷脂（各种线粒体事件的调节剂）减少。我们的研究阐明了ChREBP在脂肪组织中的新作用及其参与线粒体功能。更清楚地了解线粒体中的ChREBP可以为改善肥胖管理铺平道路。
The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that increases the transcription of multiple genes. ChREBP is highly localized in the liver, where it upregulates the expression of genes that code for glycolytic and lipogenic enzymes, resulting in the conversion of excess carbohydrate into storage fat. ChREBP knockout (KO) mice display an anti-obese phenotype. However, at this time, role of ChREBP in adipose tissue remains unclear. Therefore, the energy metabolism and morphology of mitochondrial brown adipose tissue (BAT) in ChREBP KO mice was examined. We found increased expression levels of electron transport system proteins including the mitochondrial uncoupling protein (UCP1), and mitochondrial structural alterations such as dysplasia of the cristae and the presence of small mitochondria in BAT of ChREBP KO mice. Mass spectrometry analyses revealed that fatty acid synthase was absent in the BAT of ChREBP KO mice, which probably led to a reduction in fatty acids and cardiolipin, a regulator of various mitochondrial events. Our study clarified the new role of ChREBP in adipose tissue and its involvement in mitochondrial function. A clearer understanding of ChREBP in mitochondria could pave the way for improvements in obesity management.