Author:
Han Fang,Kan Chengxia,Wu Di,Kuang Zengguang,Song Hongwei,Luo Youhong,Zhang Le,Hou Ningning,Sun Xiaodong
Abstract
Abstract
Background
Compared with typical visceral fat deposits in obesity and metabolic syndrome, perirenal adipose tissue (PRAT) dysfunction is more closely linked to obesity-related chronic kidney disease (OB-CKD). The myokine irisin reportedly promotes positive outcomes in metabolic disease. This study investigated whether irisin could reduce urinary albumin excretion and demonstrate renoprotective effects through the regulation of PRAT function in obese mice.
Methods
C57BL/6 J mice received a high-fat diet (HFD) with or without concurrent administration of irisin. Glucose tolerance, plasma levels of free fatty acids, and urinary albumin excretion were assessed, along with renal morphology. The vascular endothelial growth factor and nitric oxide in glomeruli were also analyzed, in addition to PRAT function-associated proteins.
Results
Irisin administration significantly reduced the final body weight, fat mass, and free fatty acids, without reducing PRAT mass, in HFD mice. Furthermore, irisin decreased urinary albumin excretion and attenuated both renal fibrosis and lipid accumulation. Irisin administration led to increases in PRAT function-associated proteins, including sirtuin1, uncoupling protein-1, and heme-oxygenase-1. Ex vivo treatment of PRAT and glomeruli with irisin also restored PRAT function. Finally, irisin treatment restored the vascular endothelial growth factor–nitric oxide axis.
Conclusions
Irisin attenuated metabolic disorders and protected against OB-CKD by normalizing the PRAT–kidney axis. These results suggest that agents targeting PRAT activation might be useful for treatment of OB-CKD.
Funder
Natural Science Foundation of Shandong Province of China
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Endocrinology, Diabetes and Metabolism
Cited by
6 articles.
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