Mechanisms of perirenal adipose tissue inflammation in obesity-related glomerulopathy induced by a high-fat diet in C57BL/6J mice / 中华肾脏病杂志

ABSTRACT

Objective:To evaluate perirenal adipose tissue inflammation in obesity-related glomerulopathy induced by a high-fat diet in C57BL/6J mice and further explore its probable mechanism.Methods:Twelve 8-10-week-old male C57BL/6J mice were divided into normal diet group (ND, n=6) and high-fat diet group (HFD, n=6) using simple random sampling method. After 14 weeks, the blood and kidney tissue were sampled, and the pathological change in the kidney and perirenal adipose tissue was observed by hematoxylin-eosin, periodic acid-Schiff, and Masson staining. The mRNA expression of tumor necrosis factor-α (TNF-α), M1-type macrophage marker CD11c, interleukin (IL)-1β, monocyte chemotactic protein-1 (MCP-1), IL-10, transforming growth factor-β1, M2-type macrophage marker CD206 and fibronectin 1 in perirenal fat was detected by real-time fluorescence quantitative PCR. The expression of macrophages marker F4/80, CD68 and leukocyte common antigen (LCA) in the kidney and perirenal adipose tissue was detected by immunohistochemistry. Results:After 14 weeks of feeding, compared with mice in the ND group, the weight of mice in the HFD group was significantly higher [(35.83±1.19) g vs (24.06±0.37) g, P<0.05]. In the HFD group, perirenal adipocyte hyperplasia, accompanied by glomerular hyperplasia, mesangial matrix hyperplasia and renal interstitial fibrosis, and other pathological changes was observed (all P<0.05). The level of blood glucose, blood lipid, serum creatinine and blood urea nitrogen was also significantly higher (all P<0.05). The mRNA expression of TNF-α, CD11c, IL-1β and MCP-1 related to M1 macrophages in the perirenal adipose tissue was higher (all P<0.05), and immunohistochemistry showed that the expression of F4/80, CD68 and LCA in the perirenal adipose tissue was higher in HFD group (all P<0.05). The above results showed that the number of macrophages and inflammatory cells in the perirenal adipose tissue was significantly greater in the HFD group than those in the ND group. Pearson linear correlation analysis showed that the average perirenal fat area was positively correlated with macrophages number in perirenal adipose tissue, several morphological indexes such as glomerular cross-sectional area and renal function injury indexes such as blood urea nitrogen (all P<0.05). Conclusion:The C57BL/6J mice model of obesity-related glomerulopathy induced by a high-fat diet is successfully established, and the perirenal adipose tissue shows an obvious inflammatory response, with the macrophages significantly polarized mainly in the pro-inflammatory direction towards the M1-type macrophages.