Premium
Exercise‐linked FNDC5/Irisin attenuates macrophage‐mediated renal inflammation in type 1 diabetes in aged mice
Author(s) -
Pushpakumar Sathnur,
Juin Subir Kumar,
Sen Utpal
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03859
Subject(s) - myokine , inflammation , endocrinology , medicine , fndc5 , type 2 diabetes , diabetic nephropathy , diabetes mellitus , adipose tissue , proinflammatory cytokine , macrophage polarization , macrophage , skeletal muscle , biology , extracellular matrix , biochemistry , fibronectin , microbiology and biotechnology , in vitro
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.