C1q/TNF-related protein 1 (CTRP1) is an endocrine factor with metabolic, cardiovascular, and renal functions. We previously showed that aged Ctrp1 knockout (KO) mice fed a control low-fat diet develop renal hypertrophy and dysfunction. Since aging and obesity adversely affects various organ systems, we hypothesized that aging, in combination with obesity induced by chronic high-fat feeding, would further exacerbates renal dysfunction in CTRP1-deficient animals. To test this, we fed wild-type and Ctrp1 KO mice a high-fat diet for eight months or longer. Contrary to our expectation, no differences were observed in blood pressure, heart function, or vascular stiffness between genotypes. Loss of CTRP1, however, resulted in ~2-fold renal enlargement (relative to body weight), ~60% increase in urinary total protein content and elevated pH, and changes in renal gene expression affecting metabolism, signaling, transcription, cell adhesion, solute and metabolite transport, and inflammation. Assessment of glomerular integrity, the extent of podocyte foot process effacement, as well as renal response to water restriction and salt loading did not reveal significant differences between genotypes. Interestingly, blood platelet, white blood cell, neutrophil, lymphocyte, and eosinophil counts were significantly elevated, whereas mean corpuscular volume and hemoglobin were reduced in Ctrp1-KO mice. Cytokine profiling revealed increased circulating levels of CCL17 and TIMP-1 in KO mice. Compared to our previous study, current data suggest that chronic high-fat feeding affects renal phenotypes differently than similarly aged mice fed a control low-fat diet, highlighting a diet-dependent contribution of CTRP1 deficiency to age-related changes in renal structure and function.

中文翻译：

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衰老和慢性高脂喂养对CTRP1缺陷小鼠的肾脏大小，功能和基因表达产生负面影响

C1q / TNF相关蛋白1（CTRP1）是具有代谢，心血管和肾脏功能的内分泌因子。我们以前显示，喂食对照低脂饮食的Ctrp1基因敲除（KO）老年小鼠会出现肾脏肥大和功能障碍。由于衰老和肥胖会对各种器官系统产生不利影响，因此我们假设衰老与慢性高脂喂养引起的肥胖相结合会进一步加剧CTRP1缺乏动物的肾功能不全。为了测试这一点，我们为野生型和Ctrp1 KO小鼠喂了高脂饮食八个月或更长时间。与我们的预期相反，基因型之间在血压，心脏功能或血管僵硬方面未观察到差异。然而，CTRP1的缺失导致肾脏肿大（相对于体重）增加了约2倍，尿液中总蛋白质含量增加了约60％，pH升高，以及肾脏基因表达的变化会影响新陈代谢，信号传导，转录，细胞粘附，溶质和代谢物转运以及炎症。肾小球完整性，足细胞足突消失的程度以及肾脏对水分限制和盐分负荷的反应评估并未显示出基因型之间的显着差异。有趣的是，Ctrp1-KO小鼠的血小板，白细胞，中性粒细胞，淋巴细胞和嗜酸性粒细胞计数显着升高，而平均红细胞体积和血红蛋白降低。细胞因子分析揭示了KO小鼠中CCL17和TIMP-1的循环水平增加。与我们之前的研究相比，目前的数据表明，长期高脂喂养对肾脏表型的影响与对照低脂饮食喂养的类似年龄小鼠不同，