Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain

被引：64

作者：

Fernandez, Regina F. ^{[1
]}

Kim, Sora Q. ^{[2
]}

Zhao, Yingwei ^{[2
]}

Foguth, Rachel M. ^{[3
]}

Weera, Marcus M. ^{[4
]}

Counihan, Jessica L. ^{[5
]}

Nomura, Daniel K. ^{[5
]}

Chester, Julia A. ^{[4
]}

Cannon, Jason R. ^{[3
]}

Ellis, Jessica M. ^{[1
]}

机构：

[1] East Carolina Univ, Dept Physiol, Greenville, NC 25878 USA

[2] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA

[3] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA

[4] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA

[5] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 49期

关键词：

fatty acid metabolism; neurometabolism; docosahexaenoic acid; acyl-CoA synthetase; brain lipids; POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; ASSOCIATION; ACTIVATION; EXPRESSION; RESOLUTION; MEDIATORS; INFECTION; ACSL6;

D O I：

10.1073/pnas.1807958115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly abundant in the brain and confers protection against numerous neurological diseases, yet the fundamental mechanisms regulating the enrichment of DHA in the brain remain unknown. Here, we have discovered that amember of the long-chain acyl-CoA synthetase family, Acsl6, is required for the enrichment of DHA in the brain by generating an Acsl6-deficient mouse (Acsl6(-/-)). Acsl6 is highly enriched in the brain and lipid profiling of Acsl6(-/-) tissues reveals consistent reductions in DHA-containing lipids in tissues highly abundant with Acsl6. Acsl6(-/-) mice demonstrate motor impairments, altered glutamate metabolism, and increased astrogliosis and microglia activation. In response to a neuroinflammatory lipopolysaccharide injection, Acsl6(-/-) brains show similar increases in molecular and pathological indices of astrogliosis compared with controls. These data demonstrate that Acsl6 is a key mediator of neuroprotective DHA enrichment in the brain.

引用

页码：12525 / 12530

页数：6

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