Effects of NAD⁺ Repletion with Nicotinamide Riboside on Obesity-Induced Chronic Kidney Disease and Renal Cell Lipotoxicity

Nicotinamide riboside (NR), a natural precursor of NAD⁺, has been suggested to confer protection against metabolic and age-related disorders. However, its impact on chronic kidney disease (CKD), particularly in the context of obesity, remains poorly understood. Here, we evaluated the potential effects of NR supplementation in models of obesity-induced renal injury. The metabolic and renal effects of both preventive and interventional NR supplementation were assessed in mice fed high-fat or low-fat diets. Our data showed that NAD⁺ repletion, whether preventive or interventional, did not affect body or organ weights, glucose metabolism, insulin resistance, or hepatic and renal lipid accumulation. NR supplementation was however associated with SIRT3-mediated deacetylation of SOD2 in the renal tissue of obese mice, and it moderately reduced renal dysfunction. To further explore the cellular mechanisms underlying the renal effects of NR in a lipotoxic context, we investigated its impact on renal proximal tubular cells exposed to palmitic acid (PA). NR significantly prevented oxidative stress in proximal tubular epithelial cells, as evidenced by the activation of SOD2 and the reduction of lipid peroxidation and mitochondrial dysfunction. However, NR did not reduce PA-induced lipid accumulation. In conclusion, this study provides evidence that NR exerts antioxidant effects and enhances mitochondrial function in renal cells in vitro but does not protect obese mice from metabolic disorders and associated CKD.