ω-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity
Xinyun Bi, … , Xiaoxi Li, Allan Zijian Zhao
Xinyun Bi, … , Xiaoxi Li, Allan Zijian Zhao
Published April 4, 2017
Citation Information: J Clin Invest. 2017;127(5):1757-1771. https://doi.org/10.1172/JCI87388.
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Research Article Autoimmunity Endocrinology

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

Xinyun Bi, Fanghong Li, Shanshan Liu, Yan Jin, Xin Zhang, Tao Yang, Yifan Dai, Xiaoxi Li, Allan Zijian Zhao

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Figure 6

ω-3 PUFAs have a therapeutic effect on immune infiltration in diabetic NOD mice.

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ω-3 PUFAs have a therapeutic effect on immune infiltration in diabetic N...
Confocal images (A) and quantification (B) of islets with a diameter of 50 μm that appeared adjacent to pancreatic ducts in diabetic NOD mice after lentivirus treatment and DHA plus EPA dietary intervention for 9 weeks (n = 4/group). Scale bars: 50 μm. Original magnification: ×400. **P < 0.01 versus the lenti-con group (Student’s t test). Values represent the mean ± SEM. (C) H&E-stained sections of islets from pancreatic tissue obtained from diabetic NOD mice after lentivirus treatment and DHA plus EPA dietary intervention for 9 weeks. Scale bars: 50 μm. Images are representative of 3 biological replicates. (D) Quantification of the incidence of insulitis in diabetic NOD mice after lentivirus injection or DHA plus EPA dietary intervention for 9 weeks (n = 4/group). Islets were sorted into 4 categories on the basis of the relative degree of immune infiltration: no insulitis (0), peri-insulitis (1), invasive insulitis (2), and severe insulitis (3). The differences in the incidence of no insulitis or severe insulitis between the lenti-con and lenti-mfat-1 groups (P < 0.0001) and between the DHA plus EPA and lenti-con groups (P < 0.0001) were significant. Statistical significance was determined by Pearson’s χ2 test.