Volume 29, Issue 2 (June 2025)
Physiol Pharmacol 2025, 29(2): 171-183 |
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Rahimi M R, Mahmazi S, Abbaspoor M, Rahnema M, Saifalddin D L, Ghanbari N, et al . Caffeine and exercise training alter expression of genes involved in inflammation and the browning of adipose tissue in High-Fat Diet-Fed Rats. Physiol Pharmacol 2025; 29 (2) :171-183
URL: http://ppj.phypha.ir/article-1-2350-en.html
URL: http://ppj.phypha.ir/article-1-2350-en.html
Mohammad Rahman Rahimi 
, Sanaz Mahmazi , Mehdi Abbaspoor , Mehdi Rahnema , Dara Latif Saifalddin , Nasser Ghanbari , Sarkawt Kolahdouzi , Hadi Golpasandi
, Sanaz Mahmazi , Mehdi Abbaspoor , Mehdi Rahnema , Dara Latif Saifalddin , Nasser Ghanbari , Sarkawt Kolahdouzi , Hadi Golpasandi
Abstract: (1370 Views)
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.
Keywords: Exercise training, Caffeine, Supplementation, Brown Adipose Tissue Uncoupling Protein, Inflammation
Type of Manuscript: Experimental research article |
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References
1. Blumenthal J B, Gitterman A, Ryan A S, Prior S J. Effects of exercise training and weight loss on plasma Fetuin-a levels and insulin sensitivity in overweight older men. J Diabetes Res 2017; 2017. [DOI:10.1155/2017/1492581]
2. Boström P, Wu J, Jedrychowski M P, Korde A, Ye L, Lo J C, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468. [DOI:10.1038/nature10777]
3. Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S, et al. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. Journal of Biological Chemistry 2013; 288: 28324-28330. [DOI:10.1074/jbc.C113.495473]
4. Clark K S, Coleman C, Shelton R, Heemstra L A, Novak C M. Caffeine enhances activity thermogenesis and energy expenditure in rats. Clin Exp Pharmacol Physiol 2019; 46: 475-482. [DOI:10.1111/1440-1681.13065]
5. Council N R. Guide for the care and use of laboratory animals: National Academies Press, 2010.
6. Dasgupta S, Bhattacharya S, Biswas A, Majumdar S S, Mukhopadhyay S, Ray S, et al. NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochemical journal 2010; 429: 451-462. [DOI:10.1042/BJ20100330]
7. Egan B, Carson B P, Garcia-Roves P M, Chibalin A V, Sarsfield F M, Barron N, et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor γ coactivator-1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. The Journal of physiology 2010; 588: 1779-1790. [DOI:10.1113/jphysiol.2010.188011]
8. Egan B, Zierath J R. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell metabolism 2013; 17: 162-184. [DOI:10.1016/j.cmet.2012.12.012]
9. Granata C, Oliveira R S, Little J P, Bishop D J. Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal muscle. Am J Physiol Endocrinol Metab 2020; 318: 224-236. [DOI:10.1152/ajpendo.00233.2019]
10. Høydal M A, Wisløff U, Kemi O J, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Prev Cardiol 2007; 14: 753-760. [DOI:10.1097/HJR.0b013e3281eacef1]
11. Jung T W, Youn B-S, Choi H Y, Lee S Y, Hong H C, Yang S J, et al. Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. Biochemical pharmacology 2013; 86: 960-969. [DOI:10.1016/j.bcp.2013.07.034]
12. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Frontiers in immunology 2014: 461. [DOI:10.3389/fimmu.2014.00461]
13. Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M, et al. Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 2010; 91: 950-957. [DOI:10.3945/ajcn.2009.28548]
14. Kobayashi-Hattori K, Mogi A, Matsumoto Y, Takita T. Effect of caffeine on the body fat and lipid metabolism of rats fed on a high-fat diet. Biosci Biotechnol Biochem 2005; 69: 2219-2223. [DOI:10.1271/bbb.69.2219]
15. Kogure A, Sakane N, Takakura Y, Umekawa T, Yoshioka K, Nishino H, et al. Effects of caffeine on the uncoupling protein family in obese yellow KK mice. Clin Exp Pharmacol Physiol 2002; 29: 391-394. [DOI:10.1046/j.1440-1681.2002.03675.x]
16. Lee S, Norheim F, Gulseth H L, Langleite T M, Kolnes K J, Tangen D S, et al. Interaction between plasma fetuin-A and free fatty acids predicts changes in insulin sensitivity in response to long-term exercise. Physiological reports 2017; 5: e13183. [DOI:10.14814/phy2.13183]
17. Lin X, Braymer H, Bray G, York D. Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity. Life sciences 1998; 63: 145-153. [DOI:10.1016/S0024-3205(98)00250-1]
18. Lu Y, Li H, Shen S-W, Shen Z-H, Xu M, Yang C-J, et al. Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats. Lipids Health Dis 2016; 15: 1-8. [DOI:10.1186/s12944-016-0263-y]
19. Malin S K, Mulya A, Fealy C E, Haus J M, Pagadala M R, Scelsi A R, et al. Fetuin-A is linked to improved glucose tolerance after short-term exercise training in nonalcoholic fatty liver disease. J Appl Physiol 2013; 115: 988-994. [DOI:10.1152/japplphysiol.00237.2013]
20. Miyamoto-Mikami E, Sato K, Kurihara T, Hasegawa N, Fujie S, Fujita S, et al. Endurance training-induced increase in circulating irisin levels is associated with reduction of abdominal visceral fat in middle-aged and older adults. PloS one 2015; 10: e0120354. [DOI:10.1371/journal.pone.0120354]
21. Muqaku B, Tahir A, Klepeisz P, Bileck A, Kreutz D, Mayer R L, et al. Coffee consumption modulates inflammatory processes in an individual fashion. Mol Nutr Food Res 2016; 60: 2529-2541. [DOI:10.1002/mnfr.201600328]
22. Natella F, Scaccini C. Role of coffee in modulation of diabetes risk. Nutrition reviews 2012; 70: 207-217. [DOI:10.1111/j.1753-4887.2012.00470.x]
23. Norheim F, Langleite T M, Hjorth M, Holen T, Kielland A, Stadheim H K, et al. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FASEB J 2014; 281: 739-749. [DOI:10.1111/febs.12619]
24. Ojuka E O, Jones T E, Han D H, Chen M, Holloszy J O. Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. FASEB J 2003; 17: 675-681. [DOI:10.1096/fj.02-0951com]
25. Paiva C, Beserra B, Reis C, Dorea J, Da Costa T, Amato A. Consumption of coffee or caffeine and serum concentration of inflammatory markers: A systematic review. Crit Rev Food Sci Nutr 2019; 59: 652-663. [DOI:10.1080/10408398.2017.1386159]
26. Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nature medicine 2012; 18: 1279-1285. [DOI:10.1038/nm.2851]
27. Pérez-Sotelo D, Roca-Rivada A, Larrosa-García M, Castelao C, Baamonde I, Baltar J, et al. Visceral and subcutaneous adipose tissue express and secrete functional alpha2hsglycoprotein (fetuin a) especially in obesity. Endocrine 2017; 55: 435-446. [DOI:10.1007/s12020-016-1132-1]
28. Peter P R, Park K H, Huh J Y, Wedick N M, Mantzoros C S. Circulating irisin levels are not affected by coffee intake: a randomized controlled trial. PLoS One 2014; 9: e94463. [DOI:10.1371/journal.pone.0094463]
29. Porter C, Herndon D N, Chondronikola M, Chao T, Annamalai P, Bhattarai N, et al. Human and mouse brown adipose tissue mitochondria have comparable UCP1 function. Cell metabolism 2016; 24: 246-255. [DOI:10.1016/j.cmet.2016.07.004]
30. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, et al. Evidence against a beneficial effect of irisin in humans. PloS one 2013; 8: e73680. [DOI:10.1371/journal.pone.0073680]
31. Roca-Rivada A, Castelao C, Senin L L, Landrove M O, Baltar J, Crujeiras A B, et al. FNDC5/irisin is not only a myokine but also an adipokine. PloS one 2013; 8: e60563. [DOI:10.1371/journal.pone.0060563]
32. Stepto N K, Benziane B, Wadley G D, Chibalin A V, Canny B J, Eynon N, et al. Short-term intensified cycle training alters acute and chronic responses of PGC1α and Cytochrome C oxidase IV to exercise in human skeletal muscle. PLOS one 2012; 7: e53080. [DOI:10.1371/journal.pone.0053080]
33. Timmons J A, Baar K, Davidsen P K, Atherton P J. Is irisin a human exercise gene? Nature 2012; 488: 9-10. [DOI:10.1038/nature11364]
34. Tsuchiya Y, Ando D, Goto K, Kiuchi M, Yamakita M, Koyama K. High-intensity exercise causes greater irisin response compared with low-intensity exercise under similar energy consumption. Tohoku J Exp Med 2014; 233: 135-140. [DOI:10.1620/tjem.233.135]
35. Tunc T, Aydemir G, Karaoglu A, Cekmez F, Kul M, Aydinoz S, et al. Toll-like receptor levels and caffeine responsiveness in rat pups during perinatal period. Regulatory peptides 2013; 182: 41-44. [DOI:10.1016/j.regpep.2012.12.016]
36. Tupone D, Madden C J, Morrison S F. Central activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat. Journal of Neuroscience 2013; 33: 14512-14525. [DOI:10.1523/JNEUROSCI.1980-13.2013]
37. Van Schaik L, Kettle C, Green R, Irving H R, Rathner J A. Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review. Frontiers in Neuroscience 2021: 54. [DOI:10.3389/fnins.2021.621356]
38. Vargas-Pozada E E, Ramos-Tovar E, Rodriguez-Callejas J D, Cardoso-Lezama I, Galindo-Gómez S, Talamás-Lara D, et al. Caffeine inhibits NLRP3 inflammasome activation by downregulating TLR4/MAPK/NF-κB signaling pathway in an experimental NASH model. Int J Mol Sci 2022; 23: 9954. [DOI:10.3390/ijms23179954]
39. Vettor R, Di Vincenzo A, Maffei P, Rossato M. Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction. Rev Endocr Metab Disord 2020; 21: 399-409. [DOI:10.1007/s11154-020-09565-6]
40. Villarroya F, Cereijo R, Gavaldà-Navarro A, Villarroya J, Giralt M. Inflammation of brown/beige adipose tissues in obesity and metabolic disease. J Intern Med 2018; 284: 492-504. [DOI:10.1111/joim.12803]
41. Yamada A K, Pimentel G D, Pickering C, Cordeiro A V, Silva V R. Effect of Caffeine on mitochondrial biogenesis in the skeletal muscle-a narrative review. Clinical nutrition ESPEN 2022. [DOI:10.1016/j.clnesp.2022.09.001]
42. Zhang Q, Ye R, Zhang Y-Y, Fan C-C, Wang J, Wang S, et al. Brown adipose tissue and novel management strategies for polycystic ovary syndrome therapy. Frontiers in Endocrinology 2022; 13: 847249. [DOI:10.3389/fendo.2022.847249]
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