Dietary Saturated Fatty Acids Promote Differentiation of Th1 and Th17 Cells And Aggravate Neuroinflammation (P6.149)

Abstract

OBJECTIVE: To explore possible mechanisms by which dietary factors may influence multiple sclerosis (MS) pathology. BACKGROUND: MS is an autoimmune disease of the central nervous system (CNS) involving pathogenic Th1 and Th17 cells. Environmental factors may ultimately drive the changing prevalence of the disease seen in the past half century. Recently, excess salt was identified as an environmental factor driving autoreactive Th17 responses. Epidemiological studies document a positive correlation between the incidence of MS and the intake of excess calories and saturated animal fat. DESIGN/METHODS: We investigated the influence of two different high fat diets (HFDs) in murine experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In addition, we tested the effects of the saturated fatty acid laurate (C12/0) on T cell development in vitro. RESULTS: Feeding mice a HFD containing saturated mid-chain fatty acids or saturated long chain fatty acids consistently exacerbated clinical symptoms of EAE (mid-chain HFD: n = 14 HFD vs. 13 control; long chain HFD: n = 13 HFD vs. 15 control, p < 0.05). Aggravated EAE under HFD was correlated with an increased ratio of activated (CD4⁺CD62L^low) to naïve (CD4⁺CD62L^high) T cells in the spleen, increased numbers of Th17 cells in the CNS and an increased T cell proliferation as well as interleukin-2 production in recall assays (each n = 7 p.g. p < 0.05). Laurate (500 µM) enhanced the differentiation of Th17 and Th1 cells (n = 6, p < 0.001), while it diminished regulatory T cell development (n = 6, p < 0.05). These effects were blunted in T cells conditionally deficient for the p38 alpha subunit. CONCLUSIONS: Our findings suggest that dietary saturated fatty acids may directly influence neuroinflammation in a p38 dependent manner. These data corroborate the hypothesis that nutritional habits associated with a “Western” lifestyle may contribute to MS prevalence and severity.

Disclosure: Dr. Linker has received personal compensation for activities with Bayer Pharmaceutical Corp., Biogen Idec, Novartis, Merck Serono, Teva Neuroscience as a speaker, with Biogen Idec, Novartis, and Merck Serono as a board member. Dr. Linker has received research support from Bayer Pharmaceutical Corp., Biogen Idec, Novartis, Merck Serono, and Teva Neuroscience. Dr. Kleinewietfeld has received royalty payments from Stemcell-technologies., Dr. Lee has received personal compensation for activities with Biogen Idec, Novartis. and Sanofi-Aventis Pharmaceuticals Inc. as a speaker. Dr. Muller has nothing to disclose. Dr. Manzel has nothing to disclose.