ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity

Despite the benefit of insulin, blockade of autoimmune attack and regeneration of pancreatic islets are ultimate goals for the complete cure of type 1 diabetes (T1D). Long-term consumption of omega-3 polyunsaturated fatty acids (PUFAs) is known to suppress inflammatory processes, making these fatty acids candidates for the prevention and amelioration of autoimmune diseases. Here, we explored the preventative and therapeutic effects of omega-3 PUFAs on T1D. In NOD mice, dietary intervention with omega-3 PUFAs sharply reduced the incidence of T1D, modulated the differentiation of Th cells and Tregs, and decreased the levels of IFN-gamma, IL-17, IL-6, and TNF-alpha. omega-3 PUFAs exerted similar effects on the differentiation of CD4(+) T cells isolated from human peripheral blood mononuclear cells. The regulation of CD4(+) T cell differentiation was mediated at least in part through omega-3 PUFA eicosanoid derivatives and by mTOR complex 1 (mTORC1) inhibition. Importantly, therapeutic intervention in NOD mice through nutritional supplementation or lentivirus-mediated expression of an omega-3 fatty acid desaturase, mfat-1, normalized blood glucose and insulin levels for at least 182 days, blocked the development of autoimmunity, prevented lymphocyte infiltration into regenerated islets, and sharply elevated the expression of the beta cell markers pancreatic and duodenal homeobox 1 (Pdx1) and paired box 4 (Pax4). The findings suggest that omega-3 PUFAs could potentially serve as a therapeutic modality for T1D.