Exercise-mediated amelioration of high-fat diet-induced kidney injury: implications of microRNA regulation

Obesity-related kidney injury has become a critical health concern, driven by metabolic disturbances, chronic inflammation, oxidative stress, and structural remodeling. While exercise is widely recognized for its broad health benefits, including its ability to mitigate obesity-related complications by improving metabolic homeostasis, reducing inflammation, and enhancing antioxidative capacity, its specific role in protecting renal function – particularly through the modulation of microRNAs (miRNAs) – remains insufficiently understood. This study investigated the effects of an 8-week moderate-intensity treadmill exercise intervention on high-fat diet (HFD)-induced kidney injury in a murine model. Chronic HFD feeding resulted in significant renal dysfunction, evidenced by elevated filtration markers (urinary total protein, urinary microalbumin, urinary creatinine, and serum creatinine) and injury biomarkers (neutrophil gelatinase-associated lipocalin, cystatin C, and kidney injury molecule 1), alongside structural abnormalities, such as glomerular hypertrophy, mesangial expansion, and fibrosis. These changes were accompanied by increased pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), heightened oxidative stress (elevated malondialdehyde, reduced glutathione, glutathione s-transferase, and superoxide dismutase), and dysregulation of several miRNAs, such as miR-150-5p and miR-182-5p, which are known to exacerbate renal injury. Exercise significantly alleviated the adverse effects of HFD by improving renal function, reducing structural damage, suppressing inflammation, enhancing antioxidative capacity, and downregulating miR-150-5p and miR-182-5p. These findings underscore the therapeutic potential of exercise in mitigating obesity-related kidney injury and provide novel insights into its renoprotective effects mediated by miRNA regulation.