Universidade de Sao Paulo Instituto de Ciencias Biomedicas, Departamento de Farmacologia, São Paulo, SP, Brazil.
Universidade de Sao Paulo Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brazil.
Life Sci. 2020 Sep 15;257:118061. doi: 10.1016/j.lfs.2020.118061. Epub 2020 Jul 8.
Obesity is an independent risk factor for the development of chronic kidney disease. The pathophysiology of the obesity-induced kidney injury is complex, but evidence suggests the involvement of reduced adiponectin levels and signaling. We investigated the extent by which adiponectin contributes to the establishment and progression of renal disease in wild type (WT) and adiponectin null (adipoKO) mice fed a control or a high-fat diet (HFD) for 16 weeks. HFD induced obesity, kidney hypertrophy, albuminuria, renal lipid accumulation and decreased nephrin expression in both mice genotypes. Notably, HFD in adipoKO mice exacerbated progression of albuminuria in comparison to WT mice. In addition, lack of adiponectin per se increased kidney weight, reduced nephrin levels, up-regulated Fabp4 expression, reduced Cpt1a expression and increased miR-130 levels in kidney. Our results demonstrate that lack of adiponectin combined with a HFD contributes to accelerated kidney dysfunction.
肥胖是慢性肾脏病发展的一个独立危险因素。肥胖引起的肾损伤的病理生理学机制很复杂，但有证据表明，脂联素水平和信号的降低参与其中。我们研究了脂联素在野生型（WT）和脂联素缺失（adipoKO）小鼠中对饮食诱导的肥胖、肾脏肥大、白蛋白尿、肾脏脂质积累和nephrin 表达降低的影响，这些小鼠分别喂食对照饮食或高脂肪饮食（HFD）16 周。HFD 诱导肥胖、肾脏肥大、白蛋白尿、肾脏脂质积累，并降低了两种小鼠基因型的 nephrin 表达。值得注意的是，与 WT 小鼠相比，HFD 使 adipoKO 小鼠的白蛋白尿恶化更严重。此外，脂联素的缺乏本身就会增加肾脏重量、降低 nephrin 水平、上调 Fabp4 表达、降低 Cpt1a 表达和增加肾脏中的 miR-130 水平。我们的结果表明，缺乏脂联素与 HFD 相结合会导致肾功能加速恶化。
