title: Impairment of systemic DHA synthesis affects macrophage plasticity and polarization: implications for DHA supplementation during inflammation.
abstract: Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2-/-), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2-/-mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2-/-mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2-/-mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE10691, Stockholm, Sweden.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Talamonti
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE10691, Stockholm, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Pauter
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE10691, Stockholm, Sweden.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Asadi
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE10691, Stockholm, Sweden.|European Center for Brain Research, Laboratory of Neurochemistry of Lipids, IRCCS Santa Lucia Foundation, Rome, Italy.|Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE10691, Stockholm, Sweden. anders.jacobsson@su.se.
authors.forename: Anders
authors.identifier: 0000-0001-5509-8824
authors.initials: A
authors.lastname: Jacobsson
mesh_terms: D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000276:immunology* / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000276:immunology
chemical_list: D053759:Interleukin-23; D015850:Interleukin-6; D018664:Interleukin-12; D004281:Docosahexaenoic Acids; D052247:Nitric Oxide Synthase Type II
keywords: Inflammation; Lipid metabolism; Macrophages; Omega-3