Irisin-Driven AMPK-PGC-1α Activation Underlies the Renoprotective Effects of Swimming Exercise in Obesity-Induced Kidney Injury

Background: Obesity often affects kidney health. Irisin, a myokine released during exercise, may exert renoprotective effects. This study examined the effects of swimming-induced irisin on kidney health in obese rats. Materials and methods: Sixty male rats were divided into four groups: control non-trained, obese non-trained, control trained, and obese trained. Obesity was induced using a high-fat diet, and an 8-week swimming program was implemented. Measurements included body and kidney weights, renal function markers (serum urea, creatinine, and urinary albumin), lipid profile, fasting glucose, insulin, and HOMA-IR. Levels of skeletal muscle irisin and PGC-1α were measured by ELISA, and citrate synthase activity was assessed spectrophotometrically. Renal tissue analysis included phospho-AMPKα1 (measured by ELISA), Complex I activity, ATP, Malondialdehyde (MDA), superoxide dismutase (SOD) activity (measured spectrophotometrically), and PGC-1α mRNA expression (qRT-PCR). Renal tissues were examined under a light microscope for histopathological evaluation, followed by semi-quantitative scoring of glomerular and tubulointerstitial lesions, morphometric analysis of glomerular tuft area, and a composite score of cleaved caspase-3 immunoexpression. Results: Exercise increased skeletal muscle levels of irisin, PGC-1α, and citrate synthase activity. It also activated renal AMPK, improved mitochondrial function, increased PGC-1α mRNA levels, and reduced renal oxidative stress, as evidenced by decreased malondialdehyde (MDA) levels and restored superoxide dismutase (SOD) activity in obese rats. These changes were associated with improved renal function, reduced tubular injury and apoptosis in obese rats, partial restoration of the glomerular tuft area, lower lesion scores, and reduced cleaved caspase-3 immunoexpression. Conclusions: These findings suggest that irisin may mediate the renoprotective effects of exercise through the AMPK–PGC-1α pathway, highlighting swimming as a beneficial non-pharmacological intervention and supporting a potential adjunct role for irisin in managing obesity-related CKD.