introduction: Caffeine, as a popular drink, along with exercise training, may help restore altered gene expres-sion in high-fat diet (HFD)-induced obesity. This study examined the effects of exercise training, caffeine consumption, and their interaction on inflammation and genes involved in metabolism in rats fed an HFD. Methods: Eighty male Wistar rats were separated into two groups: HFD and normal diet (ND). Each group was subsequently divided into four groups: sedentary, caffeine-only, exercise, and caffeine-plus-exercise. For eight weeks, the animals in the training groups engaged in aerobic exercise on a mo-torized treadmill for 60 minutes, five times per week. Animals in the caffeine group ingested a solution containing caffeine daily (6 mg/kg/bw). The expression of Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and fibronectin type III domain-containing (FNDC5) genes in the calf muscle, uncoupling protein-1 (UCP1) in subcutaneous adipose tissue, NF-KB and TLR4 in vis-ceral adipose tissue, and fetuin-A (Fet-A) in the liver were investigated. Results: The findings demonstrated that HFD significantly elevated the NF-Kβ gene and downregulated the skeletal muscle PGC-1α and FNDC5 genes, as well as serum fetuin-A. UCP-1 (366% vs. 56%), FNDC5 (26% vs. 54%), and PGC-1α (40% vs. 1700%) genes were all considerably elevated by exercise training and caffeine supplementation, respectively. Additionally, exercise training reduced TLR4 and NF-Kβ expression in visceral adipose tissue and liver Fet-A gene expression. Furthermore, following HFD, when compared to the sedentary group, exercise training with and without caffeine consumption decreased the NF-Kβ gene and liver Fet-A and increased PGC1-α, FNDC5, UCP1, and serum Fet-A. Conclusion: These findings support the idea that exercise and caffeine may reduce inflammation by downregulating genes involved in inflammation and adipose tissue browning.
