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Published in: BMC Medicine 1/2013

Open Access 01-12-2013 | Research article

Irisin and exercise training in humans – Results from a randomized controlled training trial

Authors: Anne Hecksteden, Melissa Wegmann, Anke Steffen, Jochen Kraushaar, Arne Morsch, Sandra Ruppenthal, Lars Kaestner, Tim Meyer

Published in: BMC Medicine | Issue 1/2013

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Abstract

Background

The recent discovery of a new myokine (irisin) potentially involved in health-related training effects has gained great attention, but evidence for a training-induced increase in irisin remains preliminary. Therefore, the present study aimed to determine whether irisin concentration is increased after regular exercise training in humans.

Methods

In a randomized controlled design, two guideline conforming training interventions were studied. Inclusion criteria were age 30 to 60 years, <1 hour/week regular activity, non-smoker, and absence of major diseases. 102 participants could be included in the analysis. Subjects in the training groups exercised 3 times per week for 26 weeks. The minimum compliance was defined at 70%. Aerobic endurance training (AET) consisted of 45 minutes of walking/running at 60% heart rate reserve. Strength endurance training (SET) consisted of 8 machine-based exercises (2 sets of 15 repetitions with 100% of the 20 repetition maximum). Serum irisin concentrations in frozen serum samples were determined in a single blinded measurement immediately after the end of the training study. Physical performance provided positive control for the overall efficacy of training. Differences between groups were tested for significance using analysis of variance. For post hoc comparisons with the control group, Dunnett’s test was used.

Results

Maximum performance increased significantly in the training groups compared with controls (controls: ±0.0 ± 0.7 km/h; AET: 1.1 ± 0.6 km/h, P < 0.01; SET: +0.5 ± 0.7 km/h, P = 0.01). Changes in irisin did not differ between groups (controls: 101 ± 81 ng/ml; AET: 44 ± 93 ng/ml; SET: 60 ± 92 ng/ml; in both cases: P = 0.99 (one-tailed testing), 1−β error probability = 0.7). The general upward trend was mainly accounted for by a negative association of irisin concentration with the storage duration of frozen serum samples (P < 0.01, β = −0.33). After arithmetically eliminating this confounder, the differences between groups remained non-significant.

Conclusions

A training-induced increase in circulating irisin could not be confirmed, calling into question its proposed involvement in health-related training effects. Because frozen samples are prone to irisin degradation over time, positive results from uncontrolled trials might exclusively reflect the longer storage of samples from initial tests.

Trial registration

Clinicaltrials.gov. Identifier: NCT01263522.
Appendix
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Literature
1.
go back to reference Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, et al: A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012, 481: 463-468. 10.1038/nature10777.CrossRefPubMedPubMedCentral Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, et al: A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012, 481: 463-468. 10.1038/nature10777.CrossRefPubMedPubMedCentral
2.
go back to reference Castillo-Quan JI: From white to brown fat through the PGC-1alpha-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech. 2012, 5: 293-295. 10.1242/dmm.009894.CrossRefPubMedPubMedCentral Castillo-Quan JI: From white to brown fat through the PGC-1alpha-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech. 2012, 5: 293-295. 10.1242/dmm.009894.CrossRefPubMedPubMedCentral
3.
4.
go back to reference Pedersen BK, Febbraio MA: Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012, 8: 457-465. 10.1038/nrendo.2012.49.CrossRefPubMed Pedersen BK, Febbraio MA: Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012, 8: 457-465. 10.1038/nrendo.2012.49.CrossRefPubMed
5.
go back to reference Sanchis-Gomar F, Lippi G, Mayero S, Perez-Quilis C, Garcia-Gimenez JL: Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes. 2012, 4: 196-10.1111/j.1753-0407.2012.00194.x.CrossRefPubMed Sanchis-Gomar F, Lippi G, Mayero S, Perez-Quilis C, Garcia-Gimenez JL: Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes. 2012, 4: 196-10.1111/j.1753-0407.2012.00194.x.CrossRefPubMed
6.
go back to reference Villarroya F: Irisin, turning up the heat. Cell Metab. 2012, 15: 277-278. 10.1016/j.cmet.2012.02.010.CrossRefPubMed Villarroya F: Irisin, turning up the heat. Cell Metab. 2012, 15: 277-278. 10.1016/j.cmet.2012.02.010.CrossRefPubMed
7.
go back to reference Crunkhorn S: Metabolic disease: exercise hormone fights metabolic disease. Nat Rev Drug Discov. 2012, 11: 189-10.1038/nrd3686.CrossRefPubMed Crunkhorn S: Metabolic disease: exercise hormone fights metabolic disease. Nat Rev Drug Discov. 2012, 11: 189-10.1038/nrd3686.CrossRefPubMed
8.
go back to reference Cunha A: Basic research: irisin-behind the benefits of exercise. Nat Rev Endocrinol. 2012, 8: 195. Cunha A: Basic research: irisin-behind the benefits of exercise. Nat Rev Endocrinol. 2012, 8: 195.
9.
go back to reference Timmons JA, Baar K, Davidsen PK, Atherton PJ: Is irisin a human exercise gene?. Nature. 2012, 488: E9-E10. 10.1038/nature11364. discussion E10-11CrossRefPubMed Timmons JA, Baar K, Davidsen PK, Atherton PJ: Is irisin a human exercise gene?. Nature. 2012, 488: E9-E10. 10.1038/nature11364. discussion E10-11CrossRefPubMed
10.
go back to reference Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS: 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. 10.1016/j.metabol.2012.09.002.CrossRefPubMedPubMedCentral Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS: 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. 10.1016/j.metabol.2012.09.002.CrossRefPubMedPubMedCentral
11.
go back to reference Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A: Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007, 116: 1081-1093.CrossRefPubMed Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A: Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007, 116: 1081-1093.CrossRefPubMed
12.
go back to reference Vanhees L, De Sutter J, Gelada SN, Doyle F, Prescott E, Cornelissen V, Kouidi E, Dugmore D, Vanuzzo D, Borjesson M, et al: Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I). Eur J Prev Cardiol. 2012, 19: 670-686. 10.1177/2047487312437059.CrossRefPubMed Vanhees L, De Sutter J, Gelada SN, Doyle F, Prescott E, Cornelissen V, Kouidi E, Dugmore D, Vanuzzo D, Borjesson M, et al: Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I). Eur J Prev Cardiol. 2012, 19: 670-686. 10.1177/2047487312437059.CrossRefPubMed
13.
go back to reference American College of Sports Medicine position stand: Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009, 41: 687-708. 10.1249/MSS.0b013e3181915670.CrossRef American College of Sports Medicine position stand: Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009, 41: 687-708. 10.1249/MSS.0b013e3181915670.CrossRef
14.
go back to reference Durnin JV, Rahaman MM: The assessment of the amount of fat in the human body from measurements of skinfold thickness. Br J Nutr. 1967, 21: 681-689. 10.1079/BJN19670070.CrossRefPubMed Durnin JV, Rahaman MM: The assessment of the amount of fat in the human body from measurements of skinfold thickness. Br J Nutr. 1967, 21: 681-689. 10.1079/BJN19670070.CrossRefPubMed
15.
go back to reference Hecksteden A, Grutters T, Meyer T: Association between postexercise hypotension and long-term training-induced blood pressure reduction: a pilot study. Clin J Sport Med. 2012, 23: 58-63.CrossRef Hecksteden A, Grutters T, Meyer T: Association between postexercise hypotension and long-term training-induced blood pressure reduction: a pilot study. Clin J Sport Med. 2012, 23: 58-63.CrossRef
16.
go back to reference Scharhag-Rosenberger F, Meyer T, Walitzek S, Kindermann W: Time course of changes in endurance capacity: a 1-yr training study. Med Sci Sports Exerc. 2009, 41: 1130-1137. 10.1249/MSS.0b013e3181935a11.CrossRefPubMed Scharhag-Rosenberger F, Meyer T, Walitzek S, Kindermann W: Time course of changes in endurance capacity: a 1-yr training study. Med Sci Sports Exerc. 2009, 41: 1130-1137. 10.1249/MSS.0b013e3181935a11.CrossRefPubMed
17.
go back to reference Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, Kim JG, Lee IK, Park KG: Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract. 2013, 100: 96-101. 10.1016/j.diabres.2013.01.007.CrossRefPubMed Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, Kim JG, Lee IK, Park KG: Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract. 2013, 100: 96-101. 10.1016/j.diabres.2013.01.007.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference Perry CG, Lally J, Holloway GP, Heigenhauser GJ, Bonen A, Spriet LL: Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010, 588: 4795-4810. 10.1113/jphysiol.2010.199448.CrossRefPubMedPubMedCentral Perry CG, Lally J, Holloway GP, Heigenhauser GJ, Bonen A, Spriet LL: Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010, 588: 4795-4810. 10.1113/jphysiol.2010.199448.CrossRefPubMedPubMedCentral
20.
go back to reference Vissing K, McGee SL, Roepstorff C, Schjerling P, Hargreaves M, Kiens B: Effect of sex differences on human MEF2 regulation during endurance exercise. Am J Physiol Endocrinol Metab. 2008, 294: E408-E415.CrossRefPubMed Vissing K, McGee SL, Roepstorff C, Schjerling P, Hargreaves M, Kiens B: Effect of sex differences on human MEF2 regulation during endurance exercise. Am J Physiol Endocrinol Metab. 2008, 294: E408-E415.CrossRefPubMed
21.
go back to reference Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ: An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1alpha and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011, 300: R1303-R1310. 10.1152/ajpregu.00538.2010.CrossRefPubMed Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ: An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1alpha and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011, 300: R1303-R1310. 10.1152/ajpregu.00538.2010.CrossRefPubMed
22.
go back to reference Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M: Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA. 2009, 106: 8665-8670. 10.1073/pnas.0903485106.CrossRefPubMedPubMedCentral Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M: Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA. 2009, 106: 8665-8670. 10.1073/pnas.0903485106.CrossRefPubMedPubMedCentral
23.
go back to reference Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ: Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol. 2009, 106: 1479-1486. 10.1152/japplphysiol.91453.2008.CrossRefPubMed Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ: Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol. 2009, 106: 1479-1486. 10.1152/japplphysiol.91453.2008.CrossRefPubMed
24.
go back to reference Saraslanidis P, Petridou A, Bogdanis GC, Galanis N, Tsalis G, Kellis S, Mougios V: Muscle metabolism and performance improvement after two training programmes of sprint running differing in rest interval duration. J Sports Sci. 2011, 29: 1167-1174. 10.1080/02640414.2011.583672.CrossRefPubMed Saraslanidis P, Petridou A, Bogdanis GC, Galanis N, Tsalis G, Kellis S, Mougios V: Muscle metabolism and performance improvement after two training programmes of sprint running differing in rest interval duration. J Sports Sci. 2011, 29: 1167-1174. 10.1080/02640414.2011.583672.CrossRefPubMed
25.
go back to reference Vind BF, Pehmoller C, Treebak JT, Birk JB, Hey-Mogensen M, Beck-Nielsen H, Zierath JR, Wojtaszewski JF, Hojlund K: Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Diabetologia. 2011, 54: 157-167. 10.1007/s00125-010-1924-4.CrossRefPubMed Vind BF, Pehmoller C, Treebak JT, Birk JB, Hey-Mogensen M, Beck-Nielsen H, Zierath JR, Wojtaszewski JF, Hojlund K: Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Diabetologia. 2011, 54: 157-167. 10.1007/s00125-010-1924-4.CrossRefPubMed
26.
go back to reference Lecker SH, Zavin A, Cao P, Arena R, Allsup K, Daniels KM, Joseph J, Schulze PC, Forman DE: Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates with Aerobic Exercise Performance in Patients with Heart Failure. Circ Heart Fail. 2012, 5: 812-818. 10.1161/CIRCHEARTFAILURE.112.969543.CrossRefPubMed Lecker SH, Zavin A, Cao P, Arena R, Allsup K, Daniels KM, Joseph J, Schulze PC, Forman DE: Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates with Aerobic Exercise Performance in Patients with Heart Failure. Circ Heart Fail. 2012, 5: 812-818. 10.1161/CIRCHEARTFAILURE.112.969543.CrossRefPubMed
27.
go back to reference Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H: Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol. 1988, 254: E248-E259.PubMed Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H: Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol. 1988, 254: E248-E259.PubMed
28.
go back to reference Pescatello LS, Kulikowich JM: The aftereffects of dynamic exercise on ambulatory blood pressure. Med Sci Sports Exerc. 2001, 33: 1855-1861. 10.1097/00005768-200111000-00009.CrossRefPubMed Pescatello LS, Kulikowich JM: The aftereffects of dynamic exercise on ambulatory blood pressure. Med Sci Sports Exerc. 2001, 33: 1855-1861. 10.1097/00005768-200111000-00009.CrossRefPubMed
29.
go back to reference Tonino RP: Effect of physical training on the insulin resistance of aging. Am J Physiol. 1989, 256: E352-E356.PubMed Tonino RP: Effect of physical training on the insulin resistance of aging. Am J Physiol. 1989, 256: E352-E356.PubMed
30.
go back to reference Meredith IT, Jennings GL, Esler MD, Dewar EM, Bruce AM, Fazio VA, Korner PI: Time-course of the antihypertensive and autonomic effects of regular endurance exercise in human subjects. J Hypertens. 1990, 8: 859-866. 10.1097/00004872-199009000-00010.CrossRefPubMed Meredith IT, Jennings GL, Esler MD, Dewar EM, Bruce AM, Fazio VA, Korner PI: Time-course of the antihypertensive and autonomic effects of regular endurance exercise in human subjects. J Hypertens. 1990, 8: 859-866. 10.1097/00004872-199009000-00010.CrossRefPubMed
31.
go back to reference Murray A, Delaney T, Bell C: Rapid onset and offset of circulatory adaptations to exercise training in men. J Hum Hypertens. 2006, 20: 193-200. 10.1038/sj.jhh.1001970.CrossRefPubMed Murray A, Delaney T, Bell C: Rapid onset and offset of circulatory adaptations to exercise training in men. J Hum Hypertens. 2006, 20: 193-200. 10.1038/sj.jhh.1001970.CrossRefPubMed
Metadata
Title
Irisin and exercise training in humans – Results from a randomized controlled training trial
Authors
Anne Hecksteden
Melissa Wegmann
Anke Steffen
Jochen Kraushaar
Arne Morsch
Sandra Ruppenthal
Lars Kaestner
Tim Meyer
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-11-235

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