Aerobic exercise attenuates ectopic renal sinus adipose tissue accumulation-related renal hypoxia injury in obese mice.

AIMS We explored the effect of aerobic exercise on renal sinus adipose (RSA) accumulation and RSA accumulation-related renal injury in obese mice. MAIN METHODS C57BL/6J male mice (n = 30) were evenly divided into three groups: control group (CON, n = 10), obese group (OB, n = 10; given high-fat diet) and obese + aerobic exercise group (OB + E, n = 10; given HFD and 8 weeks of moderate-intensity exercise training). The body weight and kidney weight were measured after sacrificing. Morphological alterations of adipose and renal tissues were measured on hematoxylin-eosin (HE) stained slides. The macrophages surface markers (F4/80, CD68, CD206, CD163), monocyte chemotactic protein 1 (MCP-1) and hypoxia inducible factor-1α (HIF-1α) were examined by immunohistochemistry assay. Inflammation-related factors (FGF-21, KIM-1, IL-6) were analyzed via serum enzyme-linked immunosorbent assay. KEY FINDINGS We found that aerobic exercise significantly reduced body weight, kidney weight, serum FGF-21 and KIM-1 levels, and ameliorated glomerular hypertrophy and RSA size accumulation in OB + E group compared with OB group. Furthermore, HIF-1α in the RSA and renal tissues was significantly increased in the OB group (P < 0.05), but exercise effectively reduced the expression of HIF-1α and ameliorated renal inflammation by reducing MCP-1 and CD68 expression (both P < 0.05), improving the conversion from M1 (CD68) to M2 (CD206, CD163) macrophages (P < 0.05), and finally alleviating the level of IL-6 (P < 0.01). SIGNIFICANCE Aerobic exercise could reduce RSA accumulation-related adipose hypoxia and macrophage infiltration, and subsequently attenuate the progress of renal injury.