High-fat diet prevents the development of autoimmune diabetes in NOD mice.

Type 1 diabetes (T1D) has a strong genetic predisposition and requires an environmental trigger to initiate the beta-cell autoimmune destruction. The rate of childhood obesity has risen in parallel to the proportion of T1D, suggesting high-fat diet (HFD)/obesity as potential environmental triggers for autoimmune diabetes. To explore this, non-obese diabetic (NOD) mice were subjected to HFD and monitored for the development of diabetes, insulitis and beta-cell stress. Four-week-old female NOD mice were placed on HFD (HFD-NOD) or standard chow-diet. Blood glucose was monitored weekly up to 40 weeks of age, and glucose- and insulin-tolerance tests performed at 4, 10 and 15 weeks. Pancreata and islets were analysed for insulin secretion, beta-cell mass, inflammation, insulitis and endoplasmic reticulum stress markers. Immune cell levels were measured in islets and spleens. Stool microbiome was analysed at age 4, 8 and 25 weeks. At early ages, HFD-NOD mice showed a significant increase in body weight, glucose intolerance and insulin resistance; but paradoxically, they were protected from developing diabetes. This was accompanied by increased insulin secretion and beta-cell mass, decreased insulitis, increased splenic T-regulatory cells and altered stool microbiome. This study shows that HFD protects NOD mice from autoimmune diabetes and preserves beta-cell mass and function through alterations in gut microbiome, increased T-regulatory cells and decreased insulitis. Further studies into the exact mechanism of HFD-mediated prevention of diabetes in NOD mice could potentially lead to interventions to prevent or delay T1D development in humans. © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Citation

Amy L Clark, Zihan Yan, Sophia X Chen, Victoria Shi, Devesha H Kulkarni, Abhinav Diwan, Maria S Remedi. High-fat diet prevents the development of autoimmune diabetes in NOD mice. Diabetes, obesity & metabolism. 2021 Nov;23(11):2455-2465

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PMID: 34212475

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