Type 2 diabetes accounts for 90% of the population with diabetes, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. The aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of the population with type 2 diabetes and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed a 45% kcal as fat diet for 8 weeks before administering streptozotocin, 30 mg/kg body weight (T2D), and compared with age- and duration-matched type 1 diabetic rats (T1D) (60 mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared with age-matched T1D rats. While at 4 months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and Rac1 promoter DNA methylation was exacerbated. At 6 months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good lifestyle and BMI could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in patients with diabetes.

中文翻译：

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饮食诱导的 2 型糖尿病大鼠模型中的视网膜病变，以及表观遗传修饰的作用

2型糖尿病占糖尿病人群的90%，这些患者普遍存在肥胖和高脂血症。除了高血糖，高血脂也与糖尿病视网膜病变密切相关。目的是在一个模型中研究视网膜病变，该模型密切模仿 2 型糖尿病人群的正常进展和代谢特征，并阐明分子机制。在给予链脲佐菌素 30 mg/kg 体重 (T2D) 之前，在喂食 45% kcal 作为脂肪饮食的大鼠中评估视网膜病变，并与年龄和持续时间匹配的 1 型糖尿病大鼠 (T1D) (60 mg/kg) 进行比较。 kg 链脲佐菌素）。在视网膜微血管系统中评估了表观遗传修饰在线粒体损伤中的作用。T2D 大鼠肥胖且严重高脂血症，与年龄匹配的 T1D 大鼠相比，葡萄糖和胰岛素耐受性受损。而在糖尿病 4 个月时，T1D 大鼠没有可检测到的视网膜病变，T2D 大鼠有明显的视网膜病变，它们的线粒体拷贝数较低，并且 mtDNA 和 Rac1 启动子 DNA 甲基化加剧。在 6 个月时，T2D 和 T1D 大鼠的视网膜病变具有可比性，这表明肥胖会加剧高血糖引起的表观遗传修饰，加速线粒体损伤和糖尿病视网膜病变。因此，维持良好的生活方式和 BMI 可能有益于调节表观遗传修饰和预防/延缓糖尿病患者的视网膜病变。mtDNA 和 Rac1 启动子 DNA 甲基化加剧。在 6 个月时，T2D 和 T1D 大鼠的视网膜病变具有可比性，这表明肥胖会加剧高血糖引起的表观遗传修饰，加速线粒体损伤和糖尿病视网膜病变。因此，维持良好的生活方式和 BMI 可能有益于调节表观遗传修饰和预防/延缓糖尿病患者的视网膜病变。mtDNA 和 Rac1 启动子 DNA 甲基化加剧。在 6 个月时，T2D 和 T1D 大鼠的视网膜病变具有可比性，这表明肥胖会加剧高血糖引起的表观遗传修饰，加速线粒体损伤和糖尿病视网膜病变。因此，维持良好的生活方式和 BMI 可能有益于调节表观遗传修饰和预防/延缓糖尿病患者的视网膜病变。