Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain
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 a member of the long-chai...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2018-12, Vol.115 (49), p.12525-12530 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Fernandez, Regina F. Kim, Sora Q. Zhao, Yingwei Foguth, Rachel M. Weera, Marcus M. Counihan, Jessica L. Nomura, Daniel K. Chester, Julia A. Cannon, Jason R. Ellis, Jessica M. |
| description | 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 a member 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. |
| doi_str_mv | 10.1073/pnas.1807958115 |
| format | Article |
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Here, we have discovered that a member 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. 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Kim, Sora Q. ; Zhao, Yingwei ; Foguth, Rachel M. ; Weera, Marcus M. ; Counihan, Jessica L. ; Nomura, Daniel K. ; Chester, Julia A. ; Cannon, Jason R. ; Ellis, Jessica M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-886957271165c343f4f1367363e9a3b2b9d1e007d56fb93e1bbc7c9f155ddf893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Biological Sciences</topic><topic>Brain</topic><topic>Brain - enzymology</topic><topic>Brain - metabolism</topic><topic>Coenzyme A Ligases - genetics</topic><topic>Coenzyme A Ligases - metabolism</topic><topic>Docosahexaenoic acid</topic><topic>Docosahexaenoic Acids - metabolism</topic><topic>Enrichment</topic><topic>Fatty acids</topic><topic>Gene Expression Regulation</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gliosis</topic><topic>Inflammation</topic><topic>Lipids</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microglia</topic><topic>Motor Activity</topic><topic>Neurodegeneration</topic><topic>Neurological diseases</topic><topic>Neuroprotection</topic><topic>SEE COMMENTARY</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernandez, Regina F.</creatorcontrib><creatorcontrib>Kim, Sora Q.</creatorcontrib><creatorcontrib>Zhao, Yingwei</creatorcontrib><creatorcontrib>Foguth, Rachel M.</creatorcontrib><creatorcontrib>Weera, Marcus M.</creatorcontrib><creatorcontrib>Counihan, Jessica L.</creatorcontrib><creatorcontrib>Nomura, Daniel K.</creatorcontrib><creatorcontrib>Chester, Julia A.</creatorcontrib><creatorcontrib>Cannon, Jason R.</creatorcontrib><creatorcontrib>Ellis, Jessica M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernandez, Regina F.</au><au>Kim, Sora Q.</au><au>Zhao, Yingwei</au><au>Foguth, Rachel M.</au><au>Weera, Marcus M.</au><au>Counihan, Jessica L.</au><au>Nomura, Daniel K.</au><au>Chester, Julia A.</au><au>Cannon, Jason R.</au><au>Ellis, Jessica M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2018-12-04</date><risdate>2018</risdate><volume>115</volume><issue>49</issue><spage>12525</spage><epage>12530</epage><pages>12525-12530</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>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. 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| subjects | Animals Biological Sciences Brain Brain - enzymology Brain - metabolism Coenzyme A Ligases - genetics Coenzyme A Ligases - metabolism Docosahexaenoic acid Docosahexaenoic Acids - metabolism Enrichment Fatty acids Gene Expression Regulation Gene Expression Regulation, Enzymologic Gliosis Inflammation Lipids Lipopolysaccharides Male Metabolism Mice Mice, Knockout Microglia Motor Activity Neurodegeneration Neurological diseases Neuroprotection SEE COMMENTARY Tissues |
| title | Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain |
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