Lipid droplet remodeling and interaction with mitochondria in mouse brown adipose tissue during cold treatment.
Lipid droplet remodeling and interaction with mitochondria in mouse brown adipose tissue during cold treatment.
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DOI：
10.1016/j.bbamcr.2015.01.020
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Jinhai Yu;Shuyan Zhang;Liujuan Cui;Weiyi Wang;Huimin Na;Xiaotong Zhu;Linghai Li;Guoheng Xu;
中科院分区：
文献类型：
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作者：
Jinhai Yu;Shuyan Zhang;Liujuan Cui;Weiyi Wang;Huimin Na;Xiaotong Zhu;Linghai Li;Guoheng Xu;
褐色脂肪组织（BAT）通过非寒颤产热来维持动物体温，这是通过解偶联蛋白1 （UCP1）来解偶联氧化磷酸化，并利用脂滴（ld）中三酰甘油（TAG）释放的脂肪酸的β-氧化。增加BAT活性和使白色脂肪组织（WAT）等其他组织“褐化”，可以增加多余储存能量的消耗，进而减少代谢性疾病的患病率。虽然许多研究已经描述了BAT和棕色脂肪细胞的生物学特性，但BAT ld特别是它们在冷暴露诱导下的激活仍有待探索。我们从小鼠肩胛间BAT中分离出ld，并使用质谱法对其进行了完整的蛋白质组学表征。形态学和生化实验均表明，ld与线粒体密切相关。冷处理小鼠BAT开始表达LD结构蛋白PLIN-2/ADRP， PLIN1表达增加。激素敏感脂肪酶（HSL）和脂肪TAG脂肪酶（ATGL）均升高。此外，离体BAT ld的线粒体蛋白UCP1水平升高，长时间的冷暴露可以刺激BAT线粒体嵴的生物发生。这些变化与转录分析的数据一致。我们的研究结果首次提供了BAT LD蛋白质组，并表明BAT LD通过将ATGL和HSL募集到细胞器，与另一种LD驻留蛋白PLIN2/ADRP的表达，以及与活化的线粒体紧密相关，偶联增加TAG水解来促进产热。这些发现将有助于研究BAT的活化以及ld与线粒体之间的相互作用。
Brown adipose tissue (BAT) maintains animal body temperature by non-shivering thermogenesis, which is through uncoupling protein 1 (UCP1) that uncouples oxidative phosphorylation and utilizes β-oxidation of fatty acids released from triacylglycerol (TAG) in lipid droplets (LDs). Increasing BAT activity and “browning” other tissues such as white adipose tissue (WAT) can enhance the expenditure of excess stored energy, and in turn reduce prevalence of metabolic diseases. Although many studies have characterized the biology of BAT and brown adipocytes, BAT LDs especially their activation induced by cold exposure remain to be explored. We have isolated LDs from mouse interscapular BAT and characterized the full proteome using mass spectrometry. Both morphological and biochemical experiments showed that the LDs could tightly associate with mitochondria. Under cold treatment mouse BAT started expressing LD structure protein PLIN-2/ADRP and increased expression of PLIN1. Both hormone sensitive lipase (HSL) and adipose TAG lipase (ATGL) were increased in LDs. In addition, isolated BAT LDs showed increased levels of the mitochondrial protein UCP1, and prolonged cold exposure could stimulate BAT mitochondrial cristae biogenesis. These changes were in agreement with the data from transcriptional analysis. Our results provide the BAT LD proteome for the first time and show that BAT LDs facilitate heat production by coupling increasing TAG hydrolysis through recruitment of ATGL and HSL to the organelle and expression of another LD resident protein PLIN2/ADRP, as well as by tightly associating with activated mitochondria. These findings will benefit the study of BAT activation and the interaction between LDs and mitochondria.