Introduction
Obesity is a fundamental problem in public health and an underlying factor in many chronic diseases and disorders [1, 2]. According to the report of the World Health Organization in 2014, 39% of adults were overweight and 13% had obesity [3]. Physical activity stimulates the production of myokines, which have different functions in skeletal muscles, fat tissue, and blood vessels [5, 6]. Irisin, as a new myokine, is the product of fibronectin type III domain-containing gene, which is mainly produced in muscles and regulated by the PGC-1 gene, and is known as a mediating factor for the beneficial effects of exercise on metabolism, with positive self-regulation [7]. In addition, irisin can reduce the body weight by improving lipid and glucose metabolism and increasing energy consumption [8]. This study aims to evaluate the effect of four weeks of ginger supplementation on irisin, insulin resistance index, and lipid profile of young women with obesity followed by eccentric and concentric training.
Materials and Methods
This is a quasi-experimental study. Participants were 50 young women with obesity. They were randomly divided into five groups. The training program included two sessions of eccentric and concentric activity on the treadmill. The subjects in the eccentric activity+supplement and concentric activity+supplement groups received one gram of ginger capsule (Xintoma) at a dose of 250 mg, two times a day (before lunch and dinner) for 4 weeks. The placebo group used capsules containing starch (placebo) during these four weeks. During supplementation, no any sports activities were performed. After the end of the supplementation, the subjects performed training (Table 1).


Blood was taken from the subjects two times, before physical activity and immediately after physical activity; each time 5 cc was taken from their brachial vein in each stage. Fasting blood samples were centrifuged at 3500 rpm.
Results
The anthropometric characteristics, body composition, and vo2max, exhausting time, and heart rate are shown in Table 1. The results of statistical tests related to irisin level, insulin level, insulin resistance index and lipid profile are given in Table 2.


The results of the correlation test of irisin level with the study variables in two types of acute eccentric and concentric exercises are shown in Table 3.


Discussion 
Based on the results of one-way ANOVA, four weeks of ginger supplementation followed by acute eccentric and concentric activity showed a significant increase in serum irisin and insulin levels and a significant decrease in glucose level compared to the placebo groups. Ginger supplement followed by acute eccentric and concentric activity also caused a significant change in levels of total cholesterol, Triglyceride, and LDL compared to the placebo groups, but no significant change was reported in the HDL level. It is possible that ginger increased thermogenesis and energy consumption through the release of catecholamines, breakdown of fat cells in white adipose tissue, and inhibition of human intestinal lumen, and which led to lipid reduction [26, 27]. Irisin is a myokine that is stimulated by acute physical activity and increases energy expenditure; thus, it has an important role in obesity and metabolic disorders, and is a potential therapeutic target in the future [12]. However, its physiology in humans remains unknown. The results of this research showed that irisin and insulin resistance of obese girls increased after both eccentric and concentric exercises. There was a significant difference between the two types of exercise in terms of irisin level, but there was no significant difference in terms of insulin resistance index. 

Ethical Considerations
Compliance with ethical guidelines
All procedures in the study on human participants were in accordance with the guidelines of the ethics committee of Ilam University of Medical Sciences (Code: IR.MEDILAM.REC.1395.192).

Funding
This study was part of a research project at Lorestan University.

Authors' contributions
Conceptualization, editing & review: Asma Soleimani, Mohammad Fathi; Investigation, sampling, and data analysis: Asma Soleimani. 

Conflicts of interest
The authors declare no conflict of interest.


References

1. Zou C, Shao J. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem. 2008; 19(5):277-86. [DOI:10.1016/j.jnutbio.2007.06.006] [PMID]
2. Batsis JA, Nieto-Martinez RE, Lopez-Jimenez F. Metabolic syndrome: From global epidemiology to individualized medicine. Clin Pharmacol Ther. 2007; 82(5):509-24. [DOI:10.1038/sj.clpt.6100355] [PMID]
3. World Health Organization (WHO). Obesity and overweight. Geneva: World Health Organization; 2016. [Link]
4. Patel S, Hoehn K, Lawrence R, Sawbridge L, Talbot N, Tomsig J, et al. Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity. Endocrinology. 2012; 153(11):5231-46. [DOI:10.1210/en.2012-1368] [PMID] [PMCID]
5. Pedersen BK. A muscular twist on the fate of fat. N Engl J Med. 2012; 366(16):1544-5. [DOI:10.1056/NEJMcibr1201024] [PMID]
6. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012; 8(8):457-65. [DOI:10.1038/nrendo.2012.49] [PMID]
7. 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]
8. Arias-Loste MT, Ranchal I, Romero-Gómez M, Crespo J. Irisin, a link among fatty liver disease, physical inactivity and insulin resistance. Int J Mol Sci. 2014; 15(12):23163-78. [DOI:10.3390/ijms151223163] [PMID] [PMCID]
9. Wu J, Ruas JL, Estall JL, Rasbach KA, Choi JH, Ye L, e al. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1α/ATF6α complex. Cell Metab. 2011; 13(2):160-9. [DOI:10.1016/j.cmet.2011.01.003] [PMID] [PMCID]
10. Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab. 2013; 98(4):E769-78. [DOI:10.1210/jc.2012-2749] [PMID]
11. Zeppetzauer M, Drexel H, Vonbank A, Rein P, Aczel S, Saely CH. Eccentric endurance exercise economically improves metabolic and inflammatory risk factors. Eur J Prev Cardiol. 2013; 20(4):577-84. [DOI:10.1177/2047487312444236] [PMID]
12. Paschalis V, Nikolaidis MG, Theodorou AA, Panayiotou G, Fatouros IG, Koutedakis Y, et al. A weekly bout of eccentric exercise is sufficient to induce health-promoting effects. Med Sci Sports Exerc. 2011; 43(1):64-73. [DOI:10.1249/MSS.0b013e3181e91d90] [PMID]
13. Wojtaszewski JF, Nielsen JN, Richter EA. Invited review: Effect of acute exercise on insulin signaling and action in humans. J Appl Physiol. 2002; 93(1):384-92. [DOI:10.1152/japplphysiol.00043.2002] [PMID]
14. Kirwan J, Del Aguila L. Insulin signalling, exercise and cellular integrity. Biochem Soc Trans. 2003; 31(Pt 6):1281-5. [DOI:10.1042/bst0311281] [PMID]
15. Wang J, Ke W, Bao R, Hu X, Chen F. Beneficial effects of ginger Zingiber officinale roscoe on obesity and metabolic syndrome: A review. Ann N Y Acad Sci. 2017; 1398(1):83-98. [DOI:10.1111/nyas.13375] [PMID]
16. Zaer Ghodsi N, Zolfaghari MR, Fattah A. The impact of high intensity interval training on lipid profile, inflamematory markers and anthropometric parameters in inactive women. Med Lab J. 2016; 10(1):56-60. [DOI:10.18869/acadpub.mlj.10.1.56]
17. Löffler D, Müller U, Scheuermann K, Friebe D, Gesing J, Bielitz J, et al. Serum irisin levels are regulated by acute strenuous exercise. J Clin Endocrinol Metab. 2015; 100(4):1289-99. [DOI:10.1210/jc.2014-2932] [PMID]
18. 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(2):135-40. [DOI:10.1620/tjem.233.135] [PMID]
19. Daskalopoulou SS, Cooke AB, Gomez YH, Mutter AF, Filippaios A, Mesfum ET, et al. Plasma irisin levels progressively increase in response to increasing exercise workloads in young, healthy, active subjects. Eur J Endocrinol. 2014; 171(3):343-52. [DOI:10.1530/EJE-14-0204] [PMID]
20. Verma SK, Singh M, Jain P, Bordia A. Protective effect of ginger, zingiber officinale Rosc on experimental atherosclerosis in rabbits. Indian J Exp Biol. 2004; 42(7):736-8. [PMID]
21. Shirdel Z, Mirbalad Zade R, Madani H. [Effect of anti diabetic and anti lipidemic of ginger in diabetic rats for aloxan mono hidrate and compare with gliben clamid (Persian)]. Iran J Diabetes Metab. 2009; 9(1):7-15. [Link]
22. Pollock ML, Foster C, Schmidt D, Hellman C, Linnerud AC, Ward A. Comparative analysis of physiologic responses to three different maximal graded exercise test protocols in healthy women. Am Heart J. 1982; 103(3):363-73. [DOI:10.1016/0002-8703(82)90275-7] [PMID]
23. Ellestad MH, Allen W, Wan MC, Kemp GL. Maximal treadmill stress testing for cardiovascular evaluation. Circulation. 1969; 39(4):517-22. [DOI:10.1161/01.CIR.39.4.517] [PMID]
24. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7):412-9. [DOI:10.1007/BF00280883] [PMID]
25. Ahn EK, Oh JS. Inhibitory effect of galanolactone isolated from Zingiber officinale roscoe extract on adipogenesis in 3T3-L1 cells. J Korean Soc Appli Biol Chem. 2012; 55:63-8. [DOI:10.1007/s13765-012-0011-6]
26. Racil G, Ben Ounis O, Hammouda O, Kallel A, Zouhal H, Chamari K, et al. Effects of high vs. moderate exercise intensity during interval training on lipids and adiponectin levels in obese young females. Eur J Appl Physiol. 2013; 113(10):2531-40. [DOI:10.1007/s00421-013-2689-5] [PMID]
27. Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, et al. FNDC5 and irisin in humans: I. predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 2012; 61(12):1725-38. [DOI:10.1016/j.metabol.2012.09.002] [PMID] [PMCID]
28. Hecksteden A, Wegmann M, Steffen A, Kraushaar J, Morsch A, Ruppenthal S, et al. Irisin and exercise training in humans-results from a randomized controlled training trial. BMC Med. 2013; 11:235. [DOI:10.1186/1741-7015-11-235] [PMID] [PMCID]

29. Shoukry A, Shalaby SM, El-Arabi Bdeer S, Mahmoud AA, Mousa MM, Khalifa A. Circulating serum irisin levels in obesity and type 2 diabetes mellitus. IUBMB Life. 2016; 68(7):544-56. [DOI:10.1002/iub.1511] [PMID]
30. Brahma Naidu P, Uddandrao VV, Ravindar Naik R, Suresh P, Meriga B, Begum MS, et al. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats. Mol Cell Endocrinol. 2016; 419:139-47. [DOI:10.1016/j.mce.2015.10.007] [PMID]
31. Gao H, Guan T, Li C, Zuo G, Yamahara J, Wang J, et al. Treatment with ginger ameliorates fructose-induced fatty liver and hypertriglyceridemia in rats: Modulation of the hepatic carbohydrate response element-binding protein-mediated pathway. Evid Based Complement Alternat Med. 2012; 2012:570948. [DOI:10.1155/2012/570948] [PMID] [PMCID]
32. Zhu J, Chen H, Song Z, Wang X, Sun Z. Effects of ginger (Zingiber officinale roscoe) on type 2 diabetes mellitus and components of the metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2018; 2018:5692962. [DOI:10.1155/2018/5692962] [PMID] [PMCID]
33. Paoli A, Pacelli QF, Moro T, Marcolin G, Neri M, Battaglia G, et al. Effects of high-intensity circuit training, low-intensity circuit training and endurance training on blood pressure and lipoproteins in middle-aged overweight men. Lipids Health Dis. 2013; 12:131. [DOI:10.1186/1476-511X-12-131] [PMID] [PMCID]
34. Hovanloo F, Shahvali Koohshoori Y, Teimoorian M, Saadati M, Fallah Huseini H. The effect of aerobic training combined and green tea (camellia sinensis l.) extract consumption on blood glucose and lipid profile in streptozotocin induced diabetic rats. J Med Plants. 2014; 13(51):84-92. [Link]
35. Elmer D. Effect of 8 weeks of high-intensity interval training versus traditional endurance training on the blood lipid profile in humans [PhD thesis]. Auburn: AUBURN University; 2013. [Link]
36. ElRokh el-SM, Yassin NA, El-Shenawy SM, Ibrahim BM. Antihypercholesterolaemic effect of ginger rhizome (Zingiber officinale) in rats. Inflammopharmacology. 2010; 18(6):309-15. [DOI:10.1007/s10787-010-0053-5] [PMID]
37. Lee JO, Kim N, Lee HJ, Moon JW, Lee SK, Kim SJ, et al. [6]-gingerol affects glucose metabolism by dual regulation via the AMPKα2-mediated AS160-Rab5 pathway and AMPK-mediated insulin sensitizing effects. J Cell Biochem. 2015; 116(7):1401-10. [DOI:10.1002/jcb.25100] [PMID]
38. Madkor HR, Mansour SW, Ramadan G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr. 2011; 105(8):1210-7. [DOI:10.1017/S0007114510004927] [PMID]
39. Priya Rani M, Padmakumari KP, Sankarikutty B, Lijo Cherian OL, Nisha VM, Raghu KG. Inhibitory potential of ginger extracts against enzymes linked to type 2 diabetes, inflammation and induced oxidative stress. Int J Food Sci Nutr. 2011; 62(2):106-10. [DOI:10.3109/09637486.2010.515565] [PMID]
40. Wei CK, Tsai YH, Korinek M, Hung PH, El-Shazly M, Cheng YB, et al. 6-Paradol and 6-Shogaol, the pungent compounds of ginger, promote glucose utilization in adipocytes and myotubes, and 6-Paradol reduces blood glucose in high-fat diet-fed mice. Int J Mol Sci. 2017; 18(1):168. [DOI:10.3390/ijms18010168] [PMID] [PMCID]
41. Rani MP, Krishna MS, Padmakumari KP, Raghu KG, Sundaresan A. Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: An in vitro study. J Sci Food Agric. 2012; 92(9):1948-55. [DOI:10.1002/jsfa.5567] [PMID]
42. Li Y, Tran VH, Duke CC, Roufogalis BD. Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes. Planta Med. 2012; 78(14):1549-55. [DOI:10.1055/s-0032-1315041] [PMID]
43. Ghanbari-Niaki A, Saghebjoo M, Soltani R, Kirwan JP. Plasma visfatin is increased after high-intensity exercise. Ann Nutr Metab. 2010; 57(1):3-8. [DOI:10.1159/000313936] [PMID]
44. Philippe M, Krüsmann PJ, Mersa L, Eder EM, Gatterer H, Melmer A, et al. Acute effects of concentric and eccentric exercise on glucose metabolism and interleukin-6 concentration in healthy males. Biol Sport. 2016; 33(2):153-8. [DOI:10.5604/20831862.1198634] [PMID] [PMCID]
45. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003; 100(14):8466-71. [DOI:10.1073/pnas.1032913100] [PMID] [PMCID]
46. Timmons JA, Baar K, Davidsen PK, Atherton PJ. Is irisin a human exercise gene? Nature. 2012; 488(7413):E9-10; discussion E10-1. [DOI:10.1038/nature11364] [PMID]
47. Yang Z, Chen X, Chen Y, Zhao Q. Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice. Int J Clin Exp Pathol. 2015; 8(6):6490-7. [PMID] [PMCID]