Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis

Publication date: 1 August 2017
Source:Cell Metabolism, Volume 26, Issue 2
Author(s): Chandramohan Chitraju, Niklas Mejhert, Joel T. Haas, L. Grisell Diaz-Ramirez, Carrie A. Grueter, Jason E. Imbriglio, Shirly Pinto, Suneil K. Koliwad, Tobias C. Walther, Robert V. Farese
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.

Graphical abstract

Teaser

Chitraju et al. unravel a decades-old mystery of why a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs during lipolysis. They show that the ER enzyme DGAT1 mediates this FA re-esterification, not to preserve TG mass but instead to protect the ER from lipotoxicity.


http://ift.tt/2wiIZWu