Neither linoleic acid nor arachidonic acid promote white adipose tissue inflammation in Fads2-/- mice fed low fat diets. (November 2017)

• Record Type: Journal Article
• Authors: Suitor, Katherine; Payne, George W.; Sarr, Ousseynou; Abdelmagid, Salma; Nakamura, Manabu T.; Ma, David WL; Mutch, David M.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 126(2017)
• Page Start: 84
• Page End: 91
• Publication Date: 2017-11
• Subjects: AA arachidonic acid -- AD ARASCO diet -- Alox-12 arachidonate 12-lipoxygenase -- Alox-15 arachidonate 15-lipoxygenase -- Ccl5 chemokine ligand 5 -- CD CORN diet -- COX cyclooxygenase -- Cox-2 cyclooxygenase-2 -- D5D delta-5-desaturase -- D6D delta-6-desaturase -- DGLA dihomo-γ-linolenic acid -- Elovl elongase -- eWAT epididymal white adipose tissue -- FA fatty acid -- Fads fatty acid desaturase -- Fads2-/- fatty acid desaturase 2 knock out -- GLA γ-linolenic acid -- iWAT inguinal white adipose tissue -- LA linoleic acid -- LOX lipoxygenase -- MAPK mitogen-activated protein kinase -- Mcp-1 monocyte chemoattractant protein-1 -- PL phospholipid -- PUFA polyunsaturated fat -- STAT signal transducer and activator of transcription -- TAG triacylglycerol -- Tnf tumour necrosis factor -- WT wild-type; Delta-6 desaturase -- Linoleic acid -- Arachidonic acid -- Inflammation -- Inguinal fat -- Epididymal fat; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2017.09.008
• Languages: English
• ISSNs: 0952-3278

Abstract

Abstract: Dietary n-6 polyunsaturated fatty acids (PUFA) are widely perceived to promote inflammation and contribute to the development of chronic diseases. This dogma has been recently questioned due to evidence that n-6 PUFA, specifically linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), do not appear to activate inflammatory signalling pathways when consumed in moderate amounts. However, delineating the independent roles of different dietary n-6 PUFA in vivo is challenging because LA is continuously converted into AA in a pathway regulated by the fatty acid desaturase 2 ( Fads2 ) gene. The objective of this study was to investigate the independent roles of LA and AA on white adipose tissue (WAT) inflammatory signalling pathways using Fads2-/- mice. We hypothesized that dietary LA would not induce WAT inflammation, unless it was endogenously converted into AA. Male C57BL/6 wild-type (WT) and Fads2-/- mice were fed low-fat isocaloric diets containing either 7% corn oil w/w (CD, containing ~42% LA) or 7% ARASCO oil w/w (AD, containing ~27% AA) for 9 weeks. WAT inflammatory gene expression, protein levels, as well as phospholipid (PL) and triacylglycerol (TAG) fatty acid composition, were analyzed by RT-qPCR, western blots, and gas chromatography, respectively. Fads2-/- mice fed CD had high LA, but little-to-no GLA (18:3n-6), DGLA (20:3n-6), and AA in PLs and TAGs compared to their WT counterparts. In comparison, Fads2-/- and WT mice fed AD showed minimal differences in n-6 PUFA content in serum and WAT, despite having significantly more AA than CD-fed mice. No differences in gene expression for common inflammatory adipokines (e.g. Mcp-1, Ccl5, Tnfα ) or key regulators of eicosanoid production (e.g. Cox-2, Alox-12, Alox-15 ) were detected in WAT between any of the diet and genotype groups. Furthermore, no differences in MCP-1, and total or phosphorylated STAT3 and p38 inflammatory proteins, were observed. Collectively, these results demonstrate that neither LA nor AA promote WAT inflammation when consumed as part of a low-fat diet. Therefore, the existing dogma surrounding n-6 PUFA and inflammation needs to be reconsidered. Highlights: Fatty acid desaturase 2 (Fads2) regulates the endogenous conversion of linoleic acid (LA) into arachidonic acid (AA). The Fads2-/- mouse is unable to convert LA into AA. Wild-type and Fads2-/- mice were fed low-fat diets enriched with either LA or AA. Neither LA nor AA increased inflammatory gene expression or protein activation in white adipose tissue. The outcomes were similar in both subcutaneous and visceral adipose tissue depots.