title: Fish-oil-derived n-3 polyunsaturated fatty acids reduce NLRP3 inflammasome activity and obesity-related inflammatory cross-talk between adipocytes and CD11b(+) macrophages.
abstract: Adipocyte-macrophage cross-talk propagates immune responses in obese adipose tissue (AT). Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) mitigate inflammation, partly through up-regulation of adiponectin; however, specific mechanisms are unclear. We determined if adipocyte-macrophage cross-talk could be mitigated by dietary LC n-3 PUFA and if this was dependent on adiponectin-mediated signaling. We utilized an in vitro co-culture model mimicking the ratio of adipocytes:macrophages in obese AT, whereby 3T3-L1 adipocytes were co-cultured with splenic CD11b(+) macrophages from C57BL/6 mice fed high-fat control (HF-CON; 34% w/w fat) or fish oil diets (HF-FO; 34% w/w fat containing 7.6% w/w FO), as well as mice fed low-fat control (LF-CON; 10% w/w fat) or FO diets (LF-FO; 10% w/w fat containing 3% w/w FO). Co-culture conditions tested effects of soluble mediator-driven mechanisms (trans-well system), cell contact and low-dose lipopolysaccharide (LPS) mimicking acute or chronic inflammatory conditions. HF-FO macrophages from acute LPS-stimulated trans-well co-cultures had decreased mRNA expression of Casp1, Il1β and Il18, as well as cellular caspase-1 activity compared to HF-CON macrophages (P≤.05). Moreover, adipocytes from acute LPS-stimulated HF-FO co-cultures had decreased caspase-1 activity and decreased IL-1β/IL-18 levels following chronic LPS pretreatment compared to HF-CON co-cultures (P≤.05). Additionally, in contact co-cultures with adiponectin-neutralizing antibody, the FO-mediated modulation of NFκB activity and decrease in phosphorylated p65 NFκB, expression of NLRP3 inflammasome genes, M1 macrophage marker genes and inflammatory cytokine/chemokine secretion were controlled partly through adiponectin, while cellular caspase-1 activity and IL-1β/1L-18 levels were decreased independently of adiponectin (P≤.05). LC n-3 PUFA may decrease the intensity of adipocyte-macrophage cross-talk to mitigate obesity-associated pathologies.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: Anna A
authors.initials: AA
authors.lastname: De Boer
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada; Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Monk
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Liddle
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Hutchinson
authors.affiliation: Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada.
authors.forename: Krista A
authors.initials: KA
authors.lastname: Power
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: David W L
authors.initials: DW
authors.lastname: Ma
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada. Electronic address: lrobinso@uoguelph.ca.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Robinson
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D039481:CD11b Antigen / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005395:Fish Oils / Q000737:chemistry / Q000627:therapeutic use; D005786:Gene Expression Regulation; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D039481:CD11b Antigen; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse
keywords: Adipocytes; Inflammatory cytokines; M1 macrophages; Obesity; Paracrine cross-talk; n-3 polyunsaturated fatty acids