Chitraju Chandramohan, Mejhert Niklas, Haas Joel T, Diaz-Ramirez L Grisell, Grueter Carrie A, Imbriglio Jason E, Pinto Shirly, Koliwad Suneil K, Walther Tobias C, Farese Robert V
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
Cell Metab. 2017 Aug 1;26(2):407-418.e3. doi: 10.1016/j.cmet.2017.07.012.
Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re-esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass but instead functions to protect the ER from lipotoxic stress and related consequences, such as adipose tissue inflammation. Our data reveal an important role for DGAT activity and TG synthesis generally in averting ER stress and lipotoxicity, with specifically DGAT1 performing this function during stimulated lipolysis in adipocytes.
甘油三酯（TG）在脂肪组织中的储存为哺乳动物提供了代谢能量的主要储备。在脂肪分解过程中，脂肪酸（FAs）从脂肪细胞的TG储存中水解出来，并转运到其他组织作为燃料。由于不明原因，脂肪细胞中很大一部分水解的FAs在一个“无效的”、消耗ATP、耗能的循环中重新酯化为TG。在这里，我们表明脂肪细胞脂肪分解过程中的FA重新酯化是由DGAT1介导的，DGAT1是一种内质网定位的DGAT酶。令人惊讶的是，这个重新酯化循环并不能保持TG的质量，而是起到保护内质网免受脂毒性应激和相关后果（如脂肪组织炎症）的作用。我们的数据揭示了DGAT活性和一般TG合成在避免内质网应激和脂毒性方面的重要作用，特别是DGAT1在脂肪细胞刺激的脂肪分解过程中发挥这一功能。
