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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 PGC1\u03b1 were detected at 8 weeks, while by 12 weeks, dysregulation extended across the entire NAD+\/Sirt1\/PGC1\u03b1 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\/PGC1\u03b1 pathway.<\/jats:p>","DOI":"10.33549\/physiolres.935706","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:37:06Z","timestamp":1784720226000},"page":"557","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Different Duration of High-Fat Feeding on the NAD+\/Sirtuins\/PGC1\u03b1 Axis in Relation to Oxidative Stress in Rat Skeletal Muscle"],"prefix":"10.33549","author":[{"given":"X","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tNutter S, Eggerichs LA, Nagpal TS, Ramos SX, Chin CC, Saiful S, et al. 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