Proinflammatory effects of arachidonic acid in a lipopolysaccharide-induced inflammatory microenvironment in 3T3-L1 adipocytes in vitro

Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have known anti-inflammatory effects, including the modulation of adipose tissue-derived inflammatory mediators (i.e., adipokines) implicated in obesity-related pathologies, such as insulin resistance. Less is known about the effects of plant-derived n-3 PUFA, α-linolenic acid (ALA, 18:3n-3) and stearidonic acid (SDA 18:4n-3), or n-6 PUFA linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), especially in combination with an inflammatory stimulus, such as lipopolysaccharide (LPS), at a dose intended to mimic obesity-associated low-grade inflammation. To study this, 3T3-L1 adipocytes were incubated with 100 μmol/L of various n-3 or n-6 PUFA with or without 10 ng/mL LPS for up to 24 h. AA in the presence of LPS synergistically increased (p < 0.05) pro-inflammatory monocyte chemoattractant protein-1 (MCP)-1 and interleukin (IL)-6 secretion and gene expression, as well as COX-2 and TLR2 gene expression at 6 and/or 24 h, suggesting their potential roles in the synergistic effects of AA and LPS. Plant-derived fatty acids ALA, SDA, and LA did not differentially affect adipokine gene expression or secretion, whereas LPS-induced pro-inflammatory IL-1β expression and MCP-1 secretion was decreased (p < 0.05) by EPA, DHA, and/or EPA+DHA (50 μmol/L each) compared with LPS alone. Only DHA increased (p < 0.05) gene expression of the n-3 PUFA receptor GPR120 and simultaneously decreased LPS-induced nuclear factor-κB activation compared with control. Our findings emphasize that specific fatty acids within the n-3 or n-6 PUFA class warrant consideration in the development of nutritional strategies to improve obesity-associated inflammation.

Keywords: 3T3-L1 adipocytes; acides gras polyinsaturés; adipocytes 3T3-L1; adipokines; endotoxemia; endotoxémie; inflammation; lipopolysaccharide; n-3; n-6; obesity; obésité; polyunsaturated fatty acids.