School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Department of Endocrinology, Shidong Hospital, Shanghai, China.
Life Sci. 2021 Aug 15;279:119106. doi: 10.1016/j.lfs.2021.119106. Epub 2021 Jan 23.
We explored the effect of aerobic exercise on renal sinus adipose (RSA) accumulation and RSA accumulation-related renal injury in obese mice.
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.
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).
Aerobic exercise could reduce RSA accumulation-related adipose hypoxia and macrophage infiltration, and subsequently attenuate the progress of renal injury.
本研究旨在探讨有氧运动对肥胖小鼠肾窦脂肪(RSA)蓄积和 RSA 蓄积相关肾损伤的影响。
将 30 只雄性 C57BL/6J 小鼠(n=30)均分为三组:对照组(CON,n=10)、肥胖组(OB,n=10,给予高脂饮食)和肥胖+有氧运动组(OB+E,n=10,给予 HFD 和 8 周的中等强度运动训练)。处死小鼠后测量体重和肾脏重量。苏木精-伊红(HE)染色切片测量脂肪和肾脏组织的形态变化。通过免疫组织化学检测巨噬细胞表面标志物(F4/80、CD68、CD206、CD163)、单核细胞趋化蛋白 1(MCP-1)和缺氧诱导因子-1α(HIF-1α)。通过血清酶联免疫吸附试验分析炎症相关因子(FGF-21、KIM-1、IL-6)。
与 OB 组相比,有氧运动显著降低了 OB+E 组的体重、肾脏重量、血清 FGF-21 和 KIM-1 水平,并改善了肾小球肥大和 RSA 大小蓄积。此外,OB 组 RSA 和肾组织中的 HIF-1α明显增加(P<0.05),但运动通过降低 MCP-1 和 CD68 表达(均 P<0.05)有效降低了 HIF-1α 的表达,改善了肾炎症,促进了 M1(CD68)向 M2(CD206、CD163)巨噬细胞的转化(均 P<0.05),最终降低了 IL-6 水平(P<0.01)。
有氧运动可减少 RSA 蓄积相关脂肪缺氧和巨噬细胞浸润,从而减轻肾损伤的进展。