Neither linoleic acid nor arachidonic acid promote white adipose tissue inflammation in Fads2-/- mice fed low fat diets

Katherine Suitor, George W. Payne, Ousseynou Sarr, Salma Abdelmagid, Manabu T. Nakamura, David WL Ma, David M. Mutch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume126
DOIs
StatePublished - Nov 2017

Keywords

  • Arachidonic acid
  • Delta-6 desaturase
  • Epididymal fat
  • Inflammation
  • Inguinal fat
  • Linoleic acid

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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