en Nervous system (others) Others Experimental research article Experimental research article <p><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction:</strong> 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.<br /> <strong>Methods:</strong> 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-acti&shy;vated receptor-gamma coactivator 1 alpha (PGC-1&alpha;) 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.<br /> <strong>Results: </strong>The findings demonstrated that HFD significantly elevated the NF-K&beta; gene and downregulated the skeletal muscle PGC-1&alpha; and FNDC5 genes, as well as serum fetuin-A. UCP-1 (366% vs. 56%), FNDC5 (26% vs. 54%), and PGC-1&alpha; (40% vs. 1700%) genes were all considerably elevated by exercise training and caffeine supplementation, respectively. Additionally, exercise training reduced TLR4 and NF-K&beta; 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-K&beta; gene and liver Fet-A and increased PGC1-&alpha;, FNDC5, UCP1, and serum Fet-A.<br /> <strong>Conclusion: </strong>These findings support the idea that exercise and caffeine may reduce inflammation by downregulating genes involved in inflammation and adipose tissue browning.</span></span></p> Exercise training, Caffeine, Supplementation, Brown Adipose Tissue Uncoupling Protein, Inflammation 171 183 http://ppj.phypha.ir/browse.php?a_code=A-10-2373-1&slc_lang=en&sid=1 Mohammad Rahman Rahimi r.rahimi@uok.ac.ir 3200319475328460037753 3200319475328460037753 Yes Department of Exercise Physiology, University of Kurdistan, Sanandaj, Iran Sanaz Mahmazi sanazmahmazi@yahoo.com 3200319475328460037754 3200319475328460037754 No Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran Mehdi Abbaspoor m.abbaspoor@uk.ac.ir 3200319475328460037755 3200319475328460037755 No Department of Physical Education and Sport Sciences, Shahid Bahonar University of Kerman, Kerman, Iran Mehdi Rahnema meh_rahnema@yahoo.com 3200319475328460037756 3200319475328460037756 No Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran Dara Latif Saifalddin dara.saifaddin@uoh.edu.iq 3200319475328460037757 3200319475328460037757 No Department of Physical Education and Sport Sciences, University of Halabja, Kurdistan region, Iraq Nasser Ghanbari naser2617@gmail.com 3200319475328460037758 3200319475328460037758 No Department of Exercise Physiology, University of Kurdistan, Sanandaj, Iran Sarkawt Kolahdouzi skolahdouzi@yahoo.com 3200319475328460037759 3200319475328460037759 No Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran Hadi Golpasandi hadi.golpasandi@uok.ac.ir 3200319475328460037760 3200319475328460037760 No Department of Exercise Physiology, University of Kurdistan, Sanandaj, Iran