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Clinical Studies and Practice

Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study

International Journal of Obesity volume 42, pages 398–404 (2018)Cite this article

Subjects

Abstract

Objective:

Animal studies have shown that irisin is a myokine secreted following physical exercise, and that it induces the remodeling of white adipose tissue toward brown adipose tissue. Therefore, a protective role of irisin against obesity, diabetes, and other metabolic and cardiovascular conditions has been hypothesized. However, data in humans are contradictory and few data are available concerning the general population.

Design:

We aimed to evaluate the association between serum irisin concentrations and habitual physical activity, as well as other metabolic and cardiovascular factors in a general population in a Mediterranean area.

Methods:

We considered 858 consecutive individuals included in the ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. Irisin serum concentrations (Phoenix Europe, Germany), habitual physical activity (HPA) level, and other blood and clinical variables were measured.

Results:

The irisin serum concentrations were not normally distributed in the cohort (Shapiro-Wilk test=0.94; P<0.001). A significant association between irisin concentrations and HPA was observed (P<0.001). Irisin concentrations were higher in women than in men (P<0.01), and significantly correlated with serum concentrations of HDL-cholesterol (P<0.05) and hs-C-reactive protein (hs-CRP; P<0.05). Binary logistic regression analysis demonstrated that high (⩾ median value) irisin serum concentrations were significantly associated with female gender (OR=1.63; 95% CI=1.16–2.28), high serum hs-CRP concentrations (OR=1.61; 95% CI=1.02–2.54) and the HPA level (OR=1.42; 95% CI=1.02–1.96).

Conclusions:

Our study confirms, in a cohort of a general population, that irisin concentrations gradually increase with the usual level of habitual physical activity.

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References

  1. Hall KD, Heymsfield SB, Kemnitz JW, Klein S, Schoeller DA, Speakman JR . Energy balance and its components: implications for body weight regulation. Am J Clin Nutr 2012; 95: 989–994.

    Article  Google Scholar 

  2. Samuel VT, Shulman GI . The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest 2016; 126: 12–22.

    Article  Google Scholar 

  3. Caballero B . The global epidemic of obesity: an overview. Epidemiol Rev 2007; 29: 1–5.

    Article  Google Scholar 

  4. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016; 387: 1513–1530.

    Article  Google Scholar 

  5. 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: 463–468.

    Article  Google Scholar 

  6. Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab 2015; 22: 734–740.

    Article  CAS  Google Scholar 

  7. 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: E769–E778.

    Article  CAS  Google Scholar 

  8. Polyzos SA, Kountouras J, Anastasilakis AD, Geladari EV, Mantzoros CS . Irisin in patients with nonalcoholic fatty liver disease. Metabolism 2014; 63: 207–217.

    Article  CAS  Google Scholar 

  9. 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: 1725–1738.

    Article  CAS  Google Scholar 

  10. Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF . Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity—correlation with body mass index. Peptides 2013; 39: 125–130.

    Article  CAS  Google Scholar 

  11. Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 2013; 98: 4899–4907.

    Article  CAS  Google Scholar 

  12. Pardo M, Crujeiras AB, Amil M, Aguera Z, Jiménez-Murcia S, Baños R et al. Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index. Int J Endocrinol 2014; 2014: 857270.

    Article  Google Scholar 

  13. Sanchis-Gomar F, Alis R, Pareja-Galeano H, Sola E, Victor VM, Rocha M et al. Circulating irisin levels are not correlated with BMI, age, and other biological parameters in obese and diabetic patients. Endocrine 2014; 46: 674–677.

    Article  CAS  Google Scholar 

  14. Al-Daghri NM, Alokail MS, Rahman S, Amer OE, Al-Attas OS, Alfawaz H et al. Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2. Eur J Clin Invest 2015; 45: 775–781.

    Article  CAS  Google Scholar 

  15. García-Fontana B, Reyes-García R, Morales-Santana S, Ávila-Rubio V, Muñoz-Garach A, Rozas-Moreno P et al. Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Endocrine 2016; 52: 54–62.

    Article  Google Scholar 

  16. Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol 2014; 592: 1091–1107.

    Article  CAS  Google Scholar 

  17. Liu JJ, Wong MD, Toy WC, Tan CS, Liu S, Ng XW et al. Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complications 2013; 27: 365–369.

    Article  Google Scholar 

  18. Oelmann S, Nauck M, Völzke H, Bahls M, Friedrich N . Circulating irisin concentrations are associated with a favourable lipid profile in the general population. PLoS One 2016; 11: e0154319.

    Article  Google Scholar 

  19. Hwang YC, Jeon WS, Park CY, Youn BS . The ratio of skeletal muscle mass to visceral fat area is a main determinant linking circulating irisin to metabolic phenotype. Cardiovasc Diabetol 2016; 15: 9.

    Article  Google Scholar 

  20. Ebert T, Focke D, Petroff D, Wurst U, Richter J, Bachmann A et al. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol 2014; 170: 501–506.

    Article  CAS  Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. Tsuchiya Y, Ando D, Takamatsu K, Goto K . Resistance exercise induces a greater irisin response than endurance exercise. Metabolism 2015; 64: 1042–1050.

    Article  CAS  Google Scholar 

  23. Huh JY, Siopi A, Mougios V, Park KH, Mantzoros CS . Irisin in response to exercise in humans with and without metabolic syndrome. J Clin Endocrinol Metab 2015; 100: 453–457.

    Article  Google Scholar 

  24. Buscemi S, Nicolucci A, Mattina A, Rosafio G, Massenti FM, Lucisano G et al. Association of dietary patterns with insulin resistance and clinically silent carotid atherosclerosis in apparently healthy people. Eur J Clin Nutr 2013; 67: 1284–1290.

    Article  CAS  Google Scholar 

  25. Buscemi S, Geraci G, Massenti FM, Buscemi C, Costa F, D’Orio C et al. Renal function and carotid atherosclerosis in adults with no known kidney disease. Nutr Metab Cardiovasc Dis 2017; 27: 267–273.

    Article  CAS  Google Scholar 

  26. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37: S81–S90.

    Article  Google Scholar 

  27. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–1645.

    Article  CAS  Google Scholar 

  28. Waist Circumference and Waist–Hip Ratio: Report of a WHO Expert Consultation Geneva, 8–11 December 2008. Available at: http://apps.who.int/iris/bitstream/10665/44583/1/9789241501491_eng.pdf.

  29. Buscemi S, Blunda G, Maneri R, Verga S . Bioelectrical characteristics of type 1 and type 2 diabetic subjects with reference to body water compartments. Acta Diabetol 1998; 35: 220–223.

    Article  CAS  Google Scholar 

  30. Goff Jr DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R et al2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. Circulation 2014; 129: S49–S73.

    Article  Google Scholar 

  31. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  Google Scholar 

  32. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.

    Article  Google Scholar 

  33. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  34. Qiu S, Cai X, Sun Z, Schumann U, Zügel M, Steinacker JM . Chronic exercise training and circulating irisin in adults: a meta-analysis. Sports Med 2015; 45: 1577–1588.

    Article  Google Scholar 

  35. 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.

    Article  Google Scholar 

  36. Blüher S, Panagiotou G, Petroff D, Markert J, Wagner A, Klemm T et al. Effects of a 1-year exercise and lifestyle intervention on irisin, adipokines, and inflammatory markers in obese children. Obesity 2014; 22: 1701–1708.

    Article  Google Scholar 

  37. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 2014; 19: 302–309.

    Article  CAS  Google Scholar 

  38. 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: 343–352.

    Article  CAS  Google Scholar 

  39. Fukushima Y, Kurose S, Shinno H, Cao Thi Thu H, Tamanoi A, Tsutsumi H et al. Relationships between serum irisin levels and metabolic parameters in Japanese patients with obesity. Obes Sci Pract 2016; 2: 203–209.

    Article  Google Scholar 

  40. Zhang Y, Xie C, Wang H, Foss RM, Clare M, George EV et al. Irisin exerts dual effects on browning and adipogenesis of human white adipocytes. Am J Physiol Endocrinol Metab 2016; 311: E530–E541.

    Article  Google Scholar 

  41. Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Belén Crujeiras A et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 2013; 8: e60563.

    Article  CAS  Google Scholar 

  42. van den Beukel JC, Grefhorst A, Hoogduijn MJ, Steenbergen J, Mastroberardino PG, FJMF Dor et al. Women have more potential to induce browning of perirenal adipose tissue than men. Obesity 2015; 23: 1671–1679.

    Article  CAS  Google Scholar 

  43. Sidebottom AC, Brown JE, Jacobs DR Jr . Pregnancy-related changes in body fat. Eur J Obstet Gynecol Reprod Biol 2001; 94: 216–223.

    Article  CAS  Google Scholar 

  44. Sohlström A, Forsum E . Changes in adipose tissue volume and distribution during reproduction in Swedish women as assessed by magnetic resonance imaging. Am J Clin Nutr 1995; 61: 287–295.

    Article  Google Scholar 

  45. Chen J, Huang Y, Gudson A, Qu S . Irisin: a new molecular marker and target in metabolic disorders. Lipids Health Dis 2015; 14: 2.

    Article  CAS  Google Scholar 

  46. Sesti G, Andreozzi F, Fiorentino TV, Mannino GC, Sciacqua A, Marini MA et al. High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects. Acta Diabetol 2014; 51: 705–713.

    Article  CAS  Google Scholar 

  47. Petersen AM, Pedersen BK . The anti-inflammatory effect of exercise. J Appl Physiol 2005; 98: 1154–1162.

    Article  CAS  Google Scholar 

  48. Matsuo Y, Gleitsmann K, Mangner N, Werner S, Fischer T, Bowen TS et al. Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines. J Cachexia Sarcopenia Muscle 2015; 6: 62–72.

    Article  Google Scholar 

  49. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY et al. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 2001; 8: 971–982.

    Article  CAS  Google Scholar 

  50. Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P et al. The myokine irisin increases cortical bone mass. Proc Natl Acad Sci USA 2015; 112: 12157–121662.

    Article  CAS  Google Scholar 

  51. Colaianni G, Mongelli T, Cuscito C, Pignataro P, Lippo L, Spiro G et al. Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice. Sci Rep 2017; 7: 2811.

    Article  Google Scholar 

  52. Erickson HP . Irisin and FNDC5 in retrospect: An exercise hormone or a transmembrane receptor? Adipocyte 2013; 2: 289–293.

    Article  CAS  Google Scholar 

  53. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L et al. Irisin - a myth rather than an exercise-inducible myokine. Sci Rep 2015; 5: 8889.

    Article  CAS  Google Scholar 

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Acknowledgements

We are gratefully indebted with Dr Antonio Nicolucci biostatistician, head of the Center for Outcomes Research and Clinical Epidemiology—CORESEARCH; Pescara, Italy (https://www.coresearch.it), for his precious advice and supervision of the statistical analyses.

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Authors and Affiliations

  1. Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS) University of Palermo (Italy) Unit of Malattie Endocrine, del Ricambio e della Nutrizione, AOU Policlinico ‘P. Giaccone’, Palermo, Italy

    S Buscemi, D Corleo, C Buscemi, A M Barile, G Rosafio, V Maniaci & C Giordano

  2. Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF),University of Palermo, Italy

    S Vasto

  3. Institute of biomedicine and molecular immunology ‘Alberto Monroy’ CNR, Palermo, Italy

    S Vasto & D Nuzzo

  4. Dipartimento di Scienze per la Promozione della Salute e Materno Infantile University of Palermo, Italy

    M F Massenti

  5. Center for Outcomes Research and Clinical Epidemiology –CORESEARCH, Pescara, Italy

    G Lucisano

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  1. S Buscemi
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Buscemi, S., Corleo, D., Vasto, S. et al. Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study. Int J Obes 42, 398–404 (2018). https://doi.org/10.1038/ijo.2017.255

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