High-fat diet prevents the development of autoimmune diabetes in NOD mice.
High-fat diet prevents the development of autoimmune diabetes in NOD mice.
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DOI：
10.1111/dom.14486
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Remedi MS
中科院分区：
文献类型：
--
作者：
Clark AL;Yan Z;Chen SX;Shi V;Kulkarni DH;Diwan A;Remedi MS
1型糖尿病（T1 D）具有很强的遗传倾向，需要环境触发来启动β细胞自身免疫破坏。儿童肥胖率与T1 D比例平行上升，表明高脂饮食（HFD）/肥胖是自身免疫性糖尿病的潜在环境触发因素。为了探索这一点，对非肥胖糖尿病（NOD）小鼠进行HFD，并监测糖尿病、胰岛炎和β细胞应激的发展。将4周龄雌性NOD小鼠置于HFD（HFD-NOD）或标准食物饮食。每周监测血糖，直至40周龄，并在第4、10和15周进行葡萄糖和胰岛素耐量试验。分析胰腺和胰岛的胰岛素分泌、β细胞群、炎症、胰岛炎和内质网应激标志物。在胰岛和脾脏中测量免疫细胞水平。分析了4周、8周和25周时的粪便微生物组。在早期，HFD‐NOD小鼠显示体重、葡萄糖耐受不良和胰岛素抵抗显著增加;但矛盾的是，它们被保护免于发展糖尿病。这伴随着胰岛素分泌和β细胞量增加，胰岛炎减少，脾脏T调节细胞增加和粪便微生物组改变。这项研究表明，HFD保护NOD小鼠免受自身免疫性糖尿病的影响，并通过改变肠道微生物组，增加T调节细胞和减少胰岛炎来保护β细胞的质量和功能。进一步研究HFD介导的NOD小鼠糖尿病预防的确切机制可能会导致干预措施，以预防或延迟人类T1 D的发展。
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.
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