For the advancement of DKD treatment, identifying unrecognized residual risk factors is essential. We explored the impact of obesity diversity derived from different carbohydrate qualities, with an emphasis on the increasing trend of excessive fructose consumption and its effect on DKD progression. In this study, we utilized mice to establish a novel diabetic model characterized by fructose overconsumption, aiming to uncover the underlying mechanisms of renal damage. Compared to the control diet group, the fructose-fed mice exhibited more pronounced obesity yet demonstrated milder glucose intolerance. Plasma cystatin C levels were elevated in the fructose model compared to the control, and this elevation was accompanied by enhanced glomerular sclerosis, even though albuminuria levels and tubular lesions were comparable. Single-cell RNA sequencing of the whole kidney highlighted an increase in Lrg1 in glomerular endothelial cells (GECs) in the fructose model, which appeared to drive mesangial fibrosis through enhanced TGF-β1 signaling. Our findings suggest that excessive fructose intake exacerbates diabetic kidney disease progression, mediated by aberrant Lrg1-driven crosstalk between GECs and mesangial cells.

中文翻译：

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果糖过量摄入会加速 db/db 小鼠肾小球内皮-系膜细胞相互作用异常的肾功能障碍

为了推进 DKD 治疗，识别未被识别的残留危险因素至关重要。我们探讨了不同碳水化合物质量对肥胖多样性的影响，重点关注过量果糖摄入的增长趋势及其对 DKD 进展的影响。在这项研究中，我们利用小鼠建立了一种以果糖过度消耗为特征的新型糖尿病模型，旨在揭示肾脏损害的潜在机制。与对照组饮食组相比，果糖喂养的小鼠表现出更明显的肥胖，但表现出更轻微的葡萄糖不耐受。与对照组相比，果糖模型中的血浆胱抑素 C 水平升高，并且这种升高伴随着肾小球硬化的增强，尽管蛋白尿水平和肾小管病变相当。全肾的单细胞 RNA 测序强调了果糖模型中肾小球内皮细胞 (GEC) 中 Lrg1 的增加，这似乎通过增强的 TGF-β1 信号传导驱动了系膜纤维化。我们的研究结果表明，过量果糖摄入会加剧糖尿病肾病的进展，这是由 GEC 和系膜细胞之间异常的 Lrg1 驱动的串扰介导的。