Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
Nutrients. 2024 Sep 12;16(18):3074. doi: 10.3390/nu16183074.
This study examined the effect of a low-carbohydrate diet (LCD) and a low-carbohydrate ketogenic diet (LCKD) on diabetic retinopathy in high-fat diet-induced diabetes mellitus in rats and studied the mechanisms of action. Rats were divided into four groups: the Control group, which was fed a normal diet for 16 weeks; the HFD group, which was fed a high-fat diet (HFD) for the first 8 weeks and then switched to a normal diet for 8 weeks; the HFD+LCD group, fed a HFD for 8 weeks followed by an LCD for 8 weeks, and the HFD+LCKD group, which was fed a HFD for 8 weeks followed by an LCKD for 8 more weeks. Both the LCD and the LCKD effectively reduced the final body and total fat weights and decreased fasting serum levels of glucose, insulin, hemoglobin A1 (HbA1C), triglycerides, cholesterol, and LDL-c. They also reduced the levels of malondialdehyde (MDA), tumor necrosis factor-α, vascular endothelial factor, caspapse-3, and bax. In the HFD rats, we found increased serum levels of β-Hydroxybutyrate and upregulated expression of Bcl2, glutathione, superoxide dismutase, and hemeoxygenase-1. Moreover, the LCD and LCKD significantly reduced mRNA levels of Kelch-like ECH-associated protein 1 (Keap1) and enhanced mRNA and nuclear concentrations of nuclear factor erythroid factor 2 (Nrf2). All these effects were associated with improved layers of the retina in the HFD - LCD and HFD + LCKD rats but not in HFD animals. The impact of the LCKD was always more profound on all measured parameters and on improving the structure of the retina compared to the LCD. In conclusion, the LCKD is superior to the LCD in preventing diabetic retinopathy in HFD-fed rats. Mechanistically, our results suggest that the hypoglycemic and hypolipidemic conditions and the Nrf2-dependent antioxidant and anti-inflammatory effects may be involved in the preventative effects of the LCD and LCKD.
本研究探讨了低碳水化合物饮食（LCD）和低碳水化合物生酮饮食（LCKD）对高脂肪饮食诱导的糖尿病大鼠糖尿病视网膜病变的影响，并研究了其作用机制。大鼠分为四组：对照组，喂食正常饮食 16 周；HFD 组，喂食高脂肪饮食（HFD）8 周，然后切换为正常饮食 8 周；HFD+LCD 组，喂食 HFD 8 周，然后喂食 LCD 8 周；HFD+LCKD 组，喂食 HFD 8 周，然后喂食 LCKD 8 周。LCD 和 LCKD 均能有效降低终体重和总脂肪重量，降低空腹血糖、胰岛素、糖化血红蛋白（HbA1C）、甘油三酯、胆固醇和 LDL-c 水平。它们还降低了丙二醛（MDA）、肿瘤坏死因子-α、血管内皮因子、caspase-3 和 bax 的水平。在 HFD 大鼠中，我们发现血清β-羟丁酸水平升高，Bcl2、谷胱甘肽、超氧化物歧化酶和血红素加氧酶-1 的表达上调。此外，LCD 和 LCKD 显著降低了 Kelch-like ECH-associated protein 1（Keap1）的 mRNA 水平，并增强了核因子红细胞因子 2（Nrf2）的 mRNA 和核浓度。所有这些影响都与 HFD-LCD 和 HFD+LCKD 大鼠视网膜层的改善有关，但与 HFD 动物无关。与 LCD 相比，LCKD 对所有测量参数和改善视网膜结构的影响总是更显著。总之，LCKD 在预防 HFD 喂养大鼠糖尿病视网膜病变方面优于 LCD。从机制上讲，我们的结果表明，低血糖、降血脂以及 Nrf2 依赖性抗氧化和抗炎作用可能参与了 LCD 和 LCKD 的预防作用。
