Effects of Different Duration of High-Fat Feeding on the NAD+/Sirtuins/PGC1alpha Axis in Relation to Oxidative Stress in Rat Skeletal Muscle.

This study examined the effects of varying durations of high-fat diet (HFD) exposure on oxidative stress and the NAD+/Sirtuins/PGC1alpha signaling pathway in rat skeletal muscle. Thirty-two male Sprague-Dawley rats were randomly assigned to either a control group or HFD groups with exposure periods of 4, 8, or 12 weeks. Outcome measures included body weight, inflammatory markers (IL-6, TNF-alpha, MCP-1), oxidative stress parameters (MDA, SOD, GSH), apoptotic activity, and protein expression levels of key components within the signaling pathway. The results demonstrated that body weight and systemic inflammation progressively increased with the duration of HFD intake. Markers of oxidative stress became significantly elevated by week 8 and further deteriorated by week 12, characterized by increased malondialdehyde (MDA) levels, diminished antioxidant capacity (reduced SOD and GSH), and enhanced apoptosis. A reduction in Sirt3 expression and increased acetylation of PGC1alpha were detected at 8 weeks, while by 12 weeks, dysregulation extended across the entire NAD+/Sirt1/PGC1alpha pathway. These alterations were associated with exacerbated oxidative damage. The findings suggest that the duration of HFD exposure plays a critical role in the development of skeletal muscle oxidative stress through progressive and time-dependent impairment of the NAD+/Sirtuins/PGC1alpha pathway. Key words High-fat diet " Skeletal muscle " Oxidative stress " Obesity " NAD+ " PGC1-alpha.