title: Cell type-specific modulation of lipid mediator's formation in murine adipose tissue by omega-3 fatty acids.
abstract: Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4.3 mg eicosapentaenoic acid and 14.7 mg docosahexaenoic acid per g of diet). Our results demonstrate selective increase in levels of anti-inflammatory lipid mediators in WAT in response to omega-3, reflecting either their association with adipocytes (endocannabinoid-related N-docosahexaenoylethanolamine) or with stromal vascular cells (pro-resolving lipid mediator protectin D1). In parallel, tissue levels of obesity-associated pro-inflammatory endocannabinoids were suppressed. Moreover, we show that adipose tissue macrophages (ATMs), which could be isolated using magnetic force from the stromal vascular fraction, are not the major producers of protectin D1 and that omega-3 PUFA lowered lipid load in ATMs while promoting their less-inflammatory phenotype. Taken together, these results further document specific roles of various cell types in WAT in control of WAT inflammation and metabolism and they suggest that also other cells but ATMs are engaged in production of pro-resolving lipid mediators in response to omega-3 PUFA.
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Kuda
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic; Charles University in Prague, Faculty of Science, Department of Analytical Chemistry, Albertov 2030, 128 43 Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Rombaldova
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Janovska
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Flachs
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: kopecky@biomed.cas.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecky
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000276:immunology; D050356:Lipid Metabolism / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D007155:Immunologic Factors
keywords: Adipose tissue macrophages; Lipid mediators; Lipidomics; Omega-3 PUFA; Protectin D1