Write your message
Volume 10, Issue 2 (9-2020)                   cmja 2020, 10(2): 106-117 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mostafavian M, Abdi A, Mehrabani J, Barari A. Effect of Eight Weeks of Aerobic Progressive Training with Capsaicin on Changes in PGC-1α and UPC-1 Expression in Visceral Adipose Tissue of Obese Rats With Diet. cmja 2020; 10 (2) :106-117
URL: http://cmja.arakmu.ac.ir/article-1-733-en.html
1- Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
2- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Guilan University, Rasht, Iran.
Full-Text [PDF 5559 kb]   (2107 Downloads)     |   Abstract (HTML)  (3216 Views)
Full-Text:   (3178 Views)

1. Introduction

Obesity is caused by an imbalance between energy intake as a result of overeating or reduced levels of physical activity. White and brown fat cells are two different types of fat cells with opposite functions. White fat is a storehouse of extra energy, while brown fat increases the oxidation of fatty acids and their production by heat through Unpaired Protein-1 (UCP-1) into the mitochondria, thereby reducing the substrate for storage in WAT [5]. The role of PGC-1α in the conversion of WAT to brown has been confirmed [8]. Increased expression of PGC-1α increases FNDC5, which breaks down from the cell membrane and is secreted into the bloodstream called irisin [8]. PGC-1α-induced irisin promotes UCP‐1 protein expression and increases mitochondrial contents. UCP‐1 is an important protein involved in the regulation of brown fat thermogenesis and the ability to convert WAT to brown adipose tissue [8]. The researchers showed that training on a treadmill increased the expression of PGC-1α [11] and UCP-1 [13]. In addition to exercise, studies have shown that the activity of brown adipose tissue with various nutrients, such as capsaicin in red pepper, increases [19]. Despite the physiological effects of capsaicin and adaptations due to long-term exercise, the simultaneous effect of exercise and capsaicin on fat phenotype change indices in the obese rat model has been less studied. Therefore, this study intends to investigate the effect of aerobic exercise with capsaicin on the expression of PGC-1α and UCP-1 gene in visceral adipose tissue in obese model mice.

2. Materials and Methods

Fourty male rats (5 weeks old, weight 147.68 9 9.41) after adaptation to environmental conditions were divided into two groups: normal diet (n=8, ND) and high fat diet (n=32, HFD). HFD rats were fed a high-fat diet for eight weeks. After eight weeks, all mice were divided into 5 groups: Normal Diet (ND), High-Fat (HFD), High-Fat-Training (HFDT), High-Fat-Capsaicin (HFDCap) and High-Fat-Training-Capsaicin (HFDTCap). Training groups have performed a progressive aerobic running program (at 15-25 m/min, 30-60 min/day, and 5 days/week) on a motor-driven treadmill for eight weeks. Capsaicin (4 mg/kg/day) were administered orally, by gavage, once a day. PGC-1α and UCP-1 gene expression levels in the VAT were measured by Real-time PCR method. For statistical analysis, ANOVA were used with a significance level set at P<0.05.

3. Results

The results of this study showed that PGC-1α (P=0.000) and UCP-1 (P=0.000) expression was decreased in HFD group compared to ND group. Also, the expression of PGC-1α and UPC-1 in HFDT (Respectively P=0.032, P=0.000), HFDCap (Respectively P=0.027, P=0.048) and HFDTCap (Respectively P=0.000, P=0.000) groups was significantly increased compared to HFD. The expression of PGC-1α and UPC-1 in HFDTCap was also significantly increased compared to HFDT (Respectively P=0.039, P=0.017) and HFDCap (Respectively P=0.046, P=0.001) groups (Table 1).

4. Discussion

In the present study, it was shown that HFD significantly reduced the expression of PGC-1α and UCP-1 in visceral adipose tissue. In this regard, Kwon et al. (2020) showed that HFD reduces the expression of UCP-1 and irisin in visceral adipose tissue and PGC-1α in skeletal muscle of obese mice [26]. Disorders of metabolism due to consumption of high-fat diet appear to reduce the expression of PGC-1α and UCP-1 in visceral adipose tissue. However, in the present study, eight weeks of progressive exercise was able to offset the negative effect of obesity on PGC-1α and UCP-1 expression. In line with this study, Ziegler et al. (2019) in a study showed that both aerobic and resistance training increase the expression of PGC-1α and UCP-1 visceral adipose tissue in rats [34]. Aerobic exercise activates adenosine monophosphate and calmodulin-dependent kinase enzymes using calcium and phosphate-dependent pathways, thereby activating PGC-1α [38]. Exercise has also been reported to increase PGC-1α expression [37], which stimulates UCP-1 expression [43]. Another result of the present study was the increased expression of PGC-1α and UCP-1 visceral adipose tissue in HFD mice after capsaicin. The findings of the present study are consistent with the finding that capsaicin is able to increase the expression of PGC-1α [20]. In addition, capsaicin is capable of enhancing several metabolic exothermic genes, including UCP-1, BMP8b, SIRT1, PGC-1α, and PRDM-16 [47]. In the present study, the additive effect of the combination of exercise and capsaicin on the expression of PGC-1α and UCP-1 was greater than the effect of each alone. Aerobic exercise and capsaicin appear to increase irisin by affecting the SIRT1/AMPK/PGC-1α signaling pathway, and increasing irisin increases UCP-1 expression in visceral adipose tissue, thereby altering WAT to brown adipose tissue.

5. Conclusion

In summary, exercise and capsaicin affected the browning of visceral adipose tissue in rats, in part due to increased expression of GC-1α and UCP-1. Therefore, the use of capsaicin and other biologically active compounds along with aerobic physical activity is an interesting effective strategy to neutralize high-fat diets.

Ethical Considerations

Compliance with ethical guidelines

This research has been carried out according to the policies related to animal protection (based on the policies of the Helsinki Convention) and with the approval of the Ethics committee in the research of the Institute of Physical Education and Sport Sciences (Code: IR.SSRC.REC.1398.125).


The present paper was extracted from the PhD. thesis of the first author, Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol. 

Authors' contributions

All authors contributed equally in all areas.

Conflicts of interest

The authors declare no conflict of interest.


The authors hereby express their gratitude to the Islamic Azad University, Ayatollah Amoli Branch.



1.Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the global burden of disease study 2013. The Lancet. 2014; 384(9945):766-81. [DOI:10.1016/S0140-6736(14)60460-8]

2.Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, et al. Obesity and severe obesity forecasts through 2030. American Journal of Preventive Medicine. 2012; 42(6):563-70. [DOI:10.1016/j.amepre.2011.10.026] [PMID]

3.Yaghoobpour Yekani O, Azarbayjani MA, Peeri M, Farzanegi P. [Effect of type of training on markers of hepatocyte apoptosis in rats fed with high fat diet (Persian)]. Yafte. 2018; 19(5):106-16. http://yafte.lums.ac.ir/article-1-2540-fa.html

4.Gonçalves IO, Passos E, Rocha-Rodrigues S, Torrella JR, Rizo D, Santos-Alves E, et al. Physical exercise antagonizes clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders. Clinical Nutrition. 2015; 34(2):241-7. [DOI:10.1016/j.clnu.2014.03.010] [PMID]

5.Harms M, Seale P. Brown and beige fat: Development, function and therapeutic potential. Nature Medicine. 2013; 19(10):1252-63. [DOI:10.1038/nm.3361] [PMID]

6.Morton TL, Galior K, McGrath C, Wu X, Uzer G, Uzer GB, et al. Exercise increases and browns muscle lipid in high-fat diet-fed mice. Frontiers in Endocrinology. 2016; 7:80. [DOI:10.3389/fendo.2016.00080] [PMID] [PMCID]

7.Servera M, López N, Serra F, Palou A. Expression of “brown-in-white” adipocyte biomarkers shows gender differences and the influence of early dietary exposure. Genes & Nutrition. 2014; 9(1):372. [DOI:10.1007/s12263-013-0372-4] [PMID] [PMCID]

8.Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481(7382):463-8. [DOI:10.1038/nature10777] [PMID] [PMCID]

9.Denjean F, Lachuer J, Géloën A, Cohen-Adad F, Moulin C, Barré H, et al. Differential regulation of uncoupling protein‐1,‐2 and ‐3 gene expression by sympathetic innervation in brown adipose tissue of thermoneutral or cold‐exposed rats. FEBS Letters. 1999; 444(2-3):181-5. [DOI:10.1016/S0014-5793(99)00056-3]

10.Kazeminasab F, Marandi SM, Ghaedi K, Safaeinejad Z, Esfarjani F, Nasr-Esfahani MH. A comparative study on the effects of high-fat diet and endurance training on the PGC-1α-FNDC5/irisin pathway in obese and nonobese male C57BL/6 mice. Applied Physiology, Nutrition, and Metabolism. 2018; 43(7):651-62. [DOI:10.1139/apnm-2017-0614] [PMID]

11.Zhang YJ, Li J, Huang W, Mo GY, Wang LH, Zhuo Y, et al. [Effect of electroacupuncture combined with treadmill exercise on body weight and expression of PGC-1α, Irisin and AMPK in skeletal muscle of diet-induced obesity rats (Chinese)]. Zhen Ci Yan Jiu. 2019; 44(7):476-80. [PMID] [DOI:10.13702/j.1000-0607.180460]

12.Kang YS, Kim JC, Kim JS, Kim SH. Effects of swimming exercise on serum Irisin and bone FNDC5 in rat models of high-fat diet-induced osteoporosis. Journal of Sports Science & Medicine. 2019; 18(4):596-603. [PMID] [PMCID]

13.Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008; 454(7203):463-9. [DOI:10.1038/nature07206] [PMID] [PMCID]

14.Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, et al. The effects of acute and chronic exercise on PGC‐1α, Irisin and browning of subcutaneous adipose tissue in humans. FEBS Journal. 2014; 281(3):739-49. [DOI:10.1111/febs.12619] [PMID]

15.Guilford BL, Parson JC, Grote CW, Vick SN, Ryals JM, Wright DE. Increased FNDC5 is associated with insulin resistance in high fat‐fed mice. Physiological Reports. 2017; 5(13):e13319. [DOI:10.14814/phy2.13319] [PMID] [PMCID]

16.Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats’ impact on whole-body energy expenditure. The Journal of Biological Chemistry. 2014; 289(49):34129-40. [DOI:10.1074/jbc.M114.591008] [PMID] [PMCID]

17.De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutrition, Metabolism & Cardiovascular Diseases. 2013; 23(6):582-90. [DOI:10.1016/j.numecd.2012.01.013] [PMID]

18.Yoneshiro T, Saito M. Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Current Opinion in Clinical Nutrition and Metabolic Care. 2013; 16(6):625-31. [DOI:10.1097/MCO.0b013e3283653ee1] [PMID]

19.Baskaran P, Krishnan V, Ren J, Thyagarajan B. Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel‐dependent mechanisms. British Journal of Pharmacology. 2016; 173(15):2369-89. [DOI:10.1111/bph.13514] [PMID] [PMCID]

20.Fan L, Xu H, Yang R, Zang Y, Chen J, Qin H. Combination of capsaicin and capsiate induces browning in 3T3-L1 white adipocytes via activation of the peroxisome proliferator-activated receptor γ/β3-adrenergic receptor signaling pathways. Journal of Agricultural and Food Chemistry. 2019; 67(22):6232-40. [DOI:10.1021/acs.jafc.9b02191] [PMID]

21.Panchal SK, Bliss E, Brown L. Capsaicin in metabolic syndrome. Nutrients. 2018; 10(5):630. [DOI:10.3390/nu10050630] [PMID] [PMCID]

22.Jamali E, Asad MR, Rassouli A. [Effect of eight-week endurance exercise on resistin gene expression in visceral adipose tissues in obese rats (Persian)]. Journal of Shahid Sadoughi University of Medical Sciences. 2017; 25(1):20-31. http://jssu.ssu.ac.ir/article-1-3559-en.html

23.Rocha-Rodrigues S, Rodríguez A, Gouveia AM, Gonçalves IO, Becerril S, Ramírez B, et al. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sciences. 2016; 165:100-8. [DOI:10.1016/j.lfs.2016.09.023] [PMID]

24.Mosqueda-Solís A, Sánchez J, Portillo MP, Palou A, Picó C. Combination of capsaicin and hesperidin reduces the effectiveness of each compound to decrease the adipocyte size and to induce browning features in adipose tissue of western diet fed rats. Journal of Agricultural and Food Chemistry. 2018; 66(37):9679-89. [DOI:10.1021/acs.jafc.8b02611] [PMID]

25.Kwon J, Kim B, Lee C, Joung H, Kim BK, Choi IS, et al. Comprehensive amelioration of high-fat diet-induced metabolic dysfunctions through activation of the PGC-1α pathway by probiotics treatment in mice. PLoS One. 2020; 15(2):e0228932. [DOI:10.1371/journal.pone.0228932] [PMID] [PMCID]

26.Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metabolism. 2005; 1(6):361-70. [DOI:10.1016/j.cmet.2005.05.004] [PMID]

27.Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998; 92(6):829-39. [DOI:10.1016/S0092-8674(00)81410-5]

28.Winn NC, Vieira-Potter VJ, Gastecki ML, Welly RJ, Scroggins RJ, Zidon TM, et al. Loss of UCP1 exacerbates western diet-induced glycemic dysregulation independent of changes in body weight in female mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017; 312(1):R74-R84. [DOI:10.1152/ajpregu.00425.2016] [PMID] [PMCID]

29.von Essen G, Lindsund E, Cannon B, Nedergaard J. Adaptive facultative diet-induced thermogenesis in wild-type but not in UCP1-ablated mice. American Journal of Physiology-Endocrinology and Metabolism. 2017; 313(5):E515-E27. [DOI:10.1152/ajpendo.00097.2017] [PMID]

30.Kim E, Lim SM, Kim MS, Yoo SH, Kim Y. Phyllodulcin, a natural sweetener, regulates obesity-related metabolic changes and fat browning-related genes of subcutaneous white adipose tissue in high-fat diet-induced obese mice. Nutrients. 2017; 9(10):1049. [DOI:10.3390/nu9101049] [PMID] [PMCID]

31.Senese R, Cioffi F, De Matteis R, Petito G, de Lange P, Silvestri E, et al. 3,5 Diiodo-L-Thyronine (T2) promotes the browning of white adipose tissue in high-fat diet-induced overweight male rats housed at thermoneutrality. Cells. 2019; 8(3):256. [DOI:10.3390/cells8030256] [PMID] [PMCID]

32.Perakakis N, Triantafyllou GA, Fernández-Real JM, Huh JY, Park KH, Seufert J, et al. Physiology and role of irisin in glucose homeostasis. Nature Reviews Endocrinology. 2017; 13(6):324-37. [DOI:10.1038/nrendo.2016.221] [PMID] [PMCID]

33.Ziegler AK, Damgaard A, Mackey AL, Schjerling P, Magnusson P, Olesen AT, et al. An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise. Scientific Reports. 2019; 9(1):12069. [DOI:10.1038/s41598-019-48587-2] [PMID] [PMCID]

34.Abdi A, Mehrabani J, Nordvall M, Wong A, Fallah A, Bagheri R. Effects of concurrent training on irisin and fibronectin type-IIi Domain Containing 5 (FNDC5) expression in visceral adipose tissue in type-2 diabetic rats. Archives of Physiology and Biochemistry. 2020; January:1-6. [DOI:10.1080/13813455.2020.1716018] [PMID]

35.Rachel Richards M, Harp JD, Ory DS, Schaffer JE. Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes. Journal of Lipid Research. 2006; 47(3):665-72. [DOI:10.1194/jlr.M500514-JLR200] [PMID]

36.Sutherland LN, Bomhof MR, Capozzi LC, Basaraba SAU, Wright DC. Exercise and adrenaline increase PGC‐1α mRNA expression in rat adipose tissue. Journal of Physiology. 2009; 587(7):1607-17. [DOI:10.1113/jphysiol.2008.165464] [PMID] [PMCID]

37.Roberts-Wilson TK, Reddy RN, Bailey JL, Zheng B, Ordas R, Gooch JL, et al. Calcineurin signaling and PGC-1α expression are suppressed during muscle atrophy due to diabetes. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2010; 1803(8):960-7. [DOI:10.1016/j.bbamcr.2010.03.019] [PMID] [PMCID]

38.Kianmehr P, Azarbayjani MA, Peeri M, Farzanegi P. Synergic effects of exercise training and octopamine on peroxisome proliferator-activated receptor-gamma coactivator-1a and uncoupling protein 1 mRNA in heart tissue of rat treated with deep frying oil. Biochemistry and Biophysics Reports. 2020; 22:100735. [DOI:10.1016/j.bbrep.2020.100735] [PMID] [PMCID]

39.Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Crujeiras AB, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013; 8(4):e60563. [DOI:10.1371/journal.pone.0060563] [PMID] [PMCID]

40.Claycombe KJ, Vomhof-DeKrey EE, Roemmich JN, Rhen T, Ghribi O. Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1-mediated thermogenesis. The Journal of Nutritional Biochemistry. 2015; 26(7):729-35. [DOI:10.1016/j.jnutbio.2015.01.008] [PMID]

41.Ghaderi M, Mohebbi H, Soltani B. [The effect of 14 weeks of endurance training with two different Intensity on serum irisin level, gene expression of skeletal muscle PGC1-α and FNDC5 and subcutaneous adipose tissue UCP1 in obese rats (Persian)]. Medical Journal of Tabriz University of Medical Sciences and Health Services. 2019; 41(1):72-81. https://mj.tbzmed.ac.ir/fa/Article/26047

42.Luisa Bonet M, Oliver P, Palou A. Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2013; 1831(5):969-85. [DOI:10.1016/j.bbalip.2012.12.002] [PMID]

43.Xing T, Kang Y, Xu X, Wang B, Du M, Zhu MJ. Raspberry supplementation improves insulin signaling and promotes brown‐like adipocyte development in white adipose tissue of obese mice. Molecular Nutrition & Food Research. 2018; 62(5):1701035. [DOI:10.1002/mnfr.201701035] [PMID]

44.Palacios-González B, Vargas-Castillo A, Velázquez-Villegas LA, Vasquez-Reyes S, López P, Noriega LG, et al. Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice. The Journal of Nutritional Biochemistry. 2019; 68:59-68. [DOI:10.1016/j.jnutbio.2019.03.012] [PMID]

45.Andrade JMO, Barcala-Jorge AS, Batista-Jorge GC, Paraíso AF, de Freitas KM, de Farias Lelis D, et al. Effect of resveratrol on expression of genes involved thermogenesis in mice and humans. Biomedicine & Pharmacotherapy. 2019; 112:108634. [DOI:10.1016/j.biopha.2019.108634] [PMID]

46.Baskaran P, Krishnan V, Fettel K, Gao P, Zhu Z, Ren J, et al. TRPV1 activation counters diet-induced obesity through sirtuin-1 activation and PRDM-16 deacetylation in brown adipose tissue. International Journal of Obesity. 2017; 41(5):739-49. [DOI:10.1038/ijo.2017.16] [PMID] [PMCID]

47.Kim SH, Plutzky J. Brown fat and browning for the treatment of obesity and related metabolic disorders. Diabetes & Metabolism Journal. 2016; 40(1):12-21. [DOI:10.4093/dmj.2016.40.1.12] [PMID] [PMCID]

48.Kida R, Yoshida H, Murakami M, Shirai M, Hashimoto O, Kawada T, et al. Direct action of capsaicin in brown adipogenesis and activation of brown adipocytes. Cell Biochemistry & Function. 2016; 34(1):34-41. [DOI:10.1002/cbf.3162] [PMID]

49.Lanzi CR, Perdicaro DJ, Tudela JG, Muscia V, Fontana AR, Oteiza PI, et al. Grape pomace extract supplementation activates FNDC5/irisin in muscle and promotes white adipose browning in rats fed a high-fat diet. Food & Function. 2020; 11(2):1537-46. [DOI:10.1039/C9FO02463H] [PMID]

50.Kong LC, Wuillemin PH, Bastard JP, Sokolovska N, Gougis S, Fellahi S, et al. Insulin resistance and inflammation predict kinetic body weight changes in response to dietary weight loss and maintenance in overweight and obese subjects by using a Bayesian network approach. The American Journal of Clinical Nutrition. 2013; 98(6):1385-94. [DOI:10.3945/ajcn.113.058099] [PMID]

Type of Study: Research | Subject: Medicinal Plants

Add your comments about this article : Your username or Email:

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Complementary Medicine Journal

Designed & Developed by : Yektaweb