Dozio Elena, Maffioli Elisa, Vianello Elena, Nonnis Simona, Grassi Scalvini Francesca, Spatola Leonardo, Roccabianca Paola, Tedeschi Gabriella, Corsi Romanelli Massimiliano Marco
Laboratory of Clinical Pathology, Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy.
Int J Mol Sci. 2022 Mar 30;23(7):3809. doi: 10.3390/ijms23073809.
The etiopathogenesis of obesity-related chronic kidney disease (CKD) is still scarcely understood. To this aim, we assessed the effect of high-fat diet (HF) on molecular pathways leading to organ damage, steatosis, and fibrosis. Six-week-old male C57BL/6N mice were fed HF diet or normal chow for 20 weeks. Kidneys were collected for genomic, proteomic, histological studies, and lipid quantification. The main findings were as follows: (1) HF diet activated specific pathways leading to fibrosis and increased fatty acid metabolism; (2) HF diet promoted a metabolic shift of lipid metabolism from peroxisomes to mitochondria; (3) no signs of lipid accumulation and/or fibrosis were observed, histologically; (4) the early signs of kidney damage seemed to be related to changes in membrane protein expression; (5) the proto-oncogene MYC was one of the upstream transcriptional regulators of changes occurring in protein expression. These results demonstrated the potential usefulness of specific selected molecules as early markers of renal injury in HF, while histomorphological changes become visible later in obesity-related CDK. The integration of these information with data from biological fluids could help the identification of biomarkers useful for the early detection and prevention of tissue damage in clinical practice.
肥胖相关慢性肾脏病（CKD）的发病机制仍鲜为人知。为此，我们评估了高脂饮食（HF）对导致器官损伤、脂肪变性和纤维化的分子途径的影响。六周龄雄性C57BL/6N小鼠分别喂食高脂饮食或正常食物20周。收集肾脏进行基因组学、蛋白质组学、组织学研究和脂质定量分析。主要研究结果如下：（1）高脂饮食激活了导致纤维化的特定途径并增加了脂肪酸代谢；（2）高脂饮食促进了脂质代谢从过氧化物酶体向线粒体的代谢转变；（3）组织学上未观察到脂质积累和/或纤维化的迹象；（4）肾脏损伤的早期迹象似乎与膜蛋白表达的变化有关；（5）原癌基因MYC是蛋白质表达发生变化的上游转录调节因子之一。这些结果证明了特定选择的分子作为高脂饮食中肾损伤早期标志物的潜在用途，而组织形态学变化在肥胖相关的CKD中较晚才可见。将这些信息与生物体液数据相结合，有助于在临床实践中识别可用于早期检测和预防组织损伤的生物标志物。
