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

被引：257

作者：

Chitraju, Chandramohan ^{[1
,2
]}

Mejhert, Niklas ^{[1
,2
]}

Haas, Joel T. ^{[5
,8
]}

Diaz-Ramirez, L. Grisell ^{[5
,9
]}

Grueter, Carrie A. ^{[10
]}

Imbriglio, Jason E. ^{[6
]}

Pinto, Shirly ^{[6
]}

Koliwad, Suneil K. ^{[5
,7
,11
]}

Walther, Tobias C. ^{[1
,2
,3
,4
]}

Farese, Robert V., Jr. ^{[1
,2
,3
]}

机构：

[1] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[3] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[4] Howard Hughes Med Inst, Boston, MA 02115 USA

[5] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA

[6] Merck & Co Inc, Kenilworth, NJ 07033 USA

[7] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[8] Univ Lille, Inst Pasteur Lille, INSERM, CHU Lille,EGID U1011, F-59000 Lille, France

[9] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA

[10] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA

[11] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

来源：

CELL METABOLISM | 2017年 / 26卷 / 02期

关键词：

ENDOPLASMIC-RETICULUM STRESS; FATTY-ACID RELEASE; DIACYLGLYCEROL ACYLTRANSFERASE; ADIPOSE-TISSUE; TRIACYLGLYCEROL SYNTHESIS; MESSENGER-RNAS; DROPLETS; OBESITY; CELLS; MICE;

D O I：

10.1016/j.cmet.2017.07.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：407 / +

页数：15

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