Diabetes Center, University of California, San Francisco, CA, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.
EMBO Rep. 2020 Sep 3;21(9):e49828. doi: 10.15252/embr.201949828. Epub 2020 Jul 16.
While brown adipose tissue (BAT) is well-recognized for its ability to dissipate energy in the form of heat, recent studies suggest multifaced roles of BAT in the regulation of glucose and lipid homeostasis beyond stimulating thermogenesis. One of the functions involves interorgan communication with metabolic organs, such as the liver, through BAT-derived secretory factors, a.k.a., batokine. However, the identity and the roles of such mediators remain insufficiently understood. Here, we employed proteomics and transcriptomics in human thermogenic adipocytes and identified previously unappreciated batokines, including phospholipid transfer protein (PLTP). We found that increased circulating levels of PLTP, via systemic or BAT-specific overexpression, significantly improve glucose tolerance and insulin sensitivity, increased energy expenditure, and decrease the circulating levels of cholesterol, phospholipids, and sphingolipids. Such changes were accompanied by increased bile acids in the circulation, which in turn enhances glucose uptake and thermogenesis in BAT. Our data suggest that PLTP is a batokine that contributes to the regulation of systemic glucose and lipid homeostasis as a mediator of BAT-liver interorgan communication.
棕色脂肪组织（BAT）以其将能量以热量形式消耗的能力而广为人知，但最近的研究表明，BAT 在调节葡萄糖和脂质稳态方面具有多方面的作用，超出了刺激产热的作用。其中一个功能涉及通过 BAT 衍生的分泌因子（即 batokine）与代谢器官（如肝脏）进行器官间通讯。然而，这些介质的身份和作用仍了解不足。在这里，我们在人类产热脂肪细胞中使用蛋白质组学和转录组学，鉴定了以前未被重视的 batokines，包括磷脂转移蛋白（PLTP）。我们发现，通过全身或 BAT 特异性过表达增加循环中的 PLTP 水平，可显著改善葡萄糖耐量和胰岛素敏感性，增加能量消耗，并降低胆固醇、磷脂和鞘脂的循环水平。这种变化伴随着循环中胆汁酸的增加，进而增强 BAT 中的葡萄糖摄取和产热。我们的数据表明，PLTP 是一种 batokine，可作为 BAT-肝脏器官间通讯的介质，有助于调节全身葡萄糖和脂质稳态。
