肌动蛋白
炎症
内分泌学
内科学
FNDC5
2型糖尿病
医学
糖尿病肾病
糖尿病
脂肪组织
促炎细胞因子
巨噬细胞极化
巨噬细胞
骨骼肌
生物
细胞外基质
体外
细胞生物学
纤维连接蛋白
生物化学
作者
Sathnur Pushpakumar,Subir Kumar Juin,Utpal Sen
标识
DOI:10.1096/fasebj.2021.35.s1.03859
摘要
Diabetes is associated with chronic low-grade inflammation in the kidney. Both classically and alternately activated macrophages play key roles in diabetic nephropathy by mediating inflammatory processes and anti-inflammatory responses respectively. Physical activity is known to modulate innate immune function, indeed exercise training is reported to reduce low-grade inflammation and improve insulin sensitivity in obese subjects. FNDC5 is a myokine secreted by skeletal muscles during exercise and the cleavage of its extracellular domain yields Irisin. In vitro studies have demonstrated that Irisin exhibits anti-inflammatory properties in adipose tissues and RAW 264.7 cells. The purpose of our study was to investigate the effect of exercise induced FNDC5/Irisin on inflammation and damage of aged kidney in type I diabetes. C57BL/6-Ins2Akita/J (Type 1 diabetes, Akita) and C57BL/6J (Wild type, WT) mice aged 54 - 56 weeks underwent 16-week exercise training of 280 m run on treadmill at speed of 7m/min. for 5 days/week for 2 weeks and increased to 12 m/min. for the remaining 14 weeks. FNDC5/Irisin was upregulated in the kidneys of WT and Akita exercise groups but to a greater magnitude in the WT. Sedentary Akita mice kidneys showed increased macrophage recruitment and M1 macrophages (CCL2, CXCL2, and CD86+/CD40+ cells) and inflammatory cytokine production. In contrast, Akita mice undergoing exercise training increased anti-inflammatory profile and M2 phenotype polarization (CD206+ cells). Exercise induced changes were associated with robust activation of AMPK and MAPK signaling in Akita mice. In comparison to sedentary group, exercise training reduced renal resistive index, improved cortical blood flow and glomerular filtration rate in WT and Akita mice. Taken together, our results suggest that exercise training and Irisin secretion protects the aged kidney from type 1 diabetes induced damage by reducing macrophage-mediated inflammation.
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