title: ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity.
abstract: 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 ω-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 ω-3 PUFAs on T1D. In NOD mice, dietary intervention with ω-3 PUFAs sharply reduced the incidence of T1D, modulated the differentiation of Th cells and Tregs, and decreased the levels of IFN-γ, IL-17, IL-6, and TNF-α. ω-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 ω-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 ω-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 β cell markers pancreatic and duodenal homeobox 1 (Pdx1) and paired box 4 (Pax4). The findings suggest that ω-3 PUFAs could potentially serve as a therapeutic modality for T1D.
authors.forename: Xinyun
authors.initials: X
authors.lastname: Bi
authors.forename: Fanghong
authors.initials: F
authors.lastname: Li
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Yifan
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.forename: Allan Zijian
authors.initials: AZ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D016688:Mice, Inbred NOD; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology
chemical_list: D001786:Blood Glucose; D015820:Cadherins; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; D015534:Trans-Activators; C502406:fat1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases