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

BMC Medicine

Tim Meyer¹  Lars Kaestner²  Sandra Ruppenthal²  Arne Morsch³  Jochen Kraushaar¹  Anke Steffen¹  Melissa Wegmann¹  Anne Hecksteden¹ 

[1] Institute of Sports and Preventive Medicine, Saarland University, 66123 Saarbrücken, Germany;Institute for Molecular Cell Biology, Saarland University, 66421 Homburg, Germany;Deutsche Hochschule für Prävention und Gesundheitsmanagement, 66123 Saarbrücken, Germany

关键词: FNDC5;    Browning;    Myokine;   

Others  :  855615
DOI  :  10.1186/1741-7015-11-235

 received in 2013-07-09, accepted in 2013-10-03,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Hecksteden et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]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.
• [2]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.
• [3]Kelly DP: Medicine. Irisin, light my fire. Science 2012, 336:42-43.
• [4]Pedersen BK, Febbraio MA: Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012, 8:457-465.
• [5]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.
• [6]Villarroya F: Irisin, turning up the heat. Cell Metab 2012, 15:277-278.
• [7]Crunkhorn S: Metabolic disease: exercise hormone fights metabolic disease. Nat Rev Drug Discov 2012, 11:189.
• [8]Cunha A: Basic research: irisin-behind the benefits of exercise. Nat Rev Endocrinol 2012, 8:195.
• [9]Timmons JA, Baar K, Davidsen PK, Atherton PJ: Is irisin a human exercise gene? Nature 2012, 488:E9-E10. discussion E10-11
• [10]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.
• [11]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.
• [12]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.
• [13]American College of Sports Medicine position stand: Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009, 41:687-708.
• [14]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.
• [15]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.
• [16]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.
• [17]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.
• [18]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.
• [19]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.
• [20]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.
• [21]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.
• [22]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.
• [23]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.
• [24]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.
• [25]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.
• [26]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.
• [27]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.
• [28]Pescatello LS, Kulikowich JM: The aftereffects of dynamic exercise on ambulatory blood pressure. Med Sci Sports Exerc 2001, 33:1855-1861.
• [29]Tonino RP: Effect of physical training on the insulin resistance of aging. Am J Physiol 1989, 256:E352-E356.
• [30]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.
• [31]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.