Cardiovascular research institute, Isfahan University of Medical Sciences ARYA Atherosclerosis Journal 1735-3955 22 Issue 2 2026 03 01 The effects of whey protein-based beverage formulation on the expression of genes related to lipid metabolisms, muscle function, and oxidative stress in trained mice 17 25 33162 10.48305/arya.2025.43538.3039 EN Alieh Abdolrezaie Department of Biochemistry, Fal.C., Islamic Azad University, Isfahan, Iran Hashem Nayeri Department of Biochemistry, Fal.C., Islamic Azad University, Isfahan, Iran 0000-0002-4334-9064 Ali Mohammad Ahadi Department of Genetics, School of Science, Shahr-e-Kord University, Shahr-e-Kord, Iran Ali Nasirpour Department of Food Science and Technology, Isfahan University of Technology, Isfahan, Iran Ahmad Bagheri Moghadam Isfahan Sport Medicine Board, Isfahan, Iran Journal Article 2025 04 28 <strong>BACKGROUND:</strong> The expression of metabolic genes can be changed by the simultaneous effect of endurance exercise and nutrition. The aim of this study was to verify the effects of endurance exercise and whey protein consumption on the expression of Fibronectin type III domain-containing protein 5 (FNDC5), Paraoxonase-1 (PON1), and proliferator-activated receptor alpha (PPARα) genes in muscle.<br><strong>METHODS:</strong> A total of twenty BalB/C male mice were accidentally selected and subsequently divided into four groups, with each group consisting of five mice. The groups were as follows: placebo, exercised, whey-supplemented, and exercise plus whey-supplemented. In the groups involving exercise, the animals underwent treadmill exercise three times per week. The expression of FNDC5, PON1, and PPARα genes was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, GraphPad Prism 9.0 software was used to statistically evaluate changes in gene expression, and one-way analysis of variance (ANOVA) at the p<0.05 level and Tukey’s multiple comparison test.<br><strong>RESULTS: </strong>FNDC5 gene expression in muscle increased in the groups that were supplemented with whey or exercised, compared to the placebo group. Investigations did not show a significant difference in FNDC5 expression in the liver between the whey-supplemented, exercise plus whey-supplemented, and placebo groups. In both liver and muscle tissue, whey protein increased the expression of PON1 (P = 0.001) regardless of exercise. PPARα expression also increased in muscle tissue. Additionally, the expression of PON1 in muscle was higher in the whey-supplemented group compared to the exercise and placebo groups.<br><strong>CONCLUSION: </strong>The consumption of whey protein and its interaction with exercise can significantly contribute to the modification of energy and lipid metabolism, muscle function, and oxidative stress through increased metabolic gene transcription. https://arya.mui.ac.ir/article_33162_30fb29ade62fcc64db06d1001676c913.pdf