Effect of endurance training on skeletal muscle myokine expression in obese men: Identification of apelin as a novel myokine

1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
International journal of obesity (2005) (Impact Factor: 5). 08/2013; 38(5). DOI: 10.1038/ijo.2013.158
Source: PubMed


IntroductionIt has been suggested that metabolic benefits of physical exercise could be mediated by myokines. We examined here the effect of exercise training on skeletal muscle expression of a panel of myokines in humans. Pathways regulating myokine expression were investigated in human myotubes.Methods
Eleven obese non diabetic male subjects were enrolled in an 8-week endurance training program. Insulin sensitivity was assessed by oral glucose tolerance test. Subcutaneous adipose tissue and Vastus Lateralis muscle biopsies were collected before and after training. RNAs were prepared from adipose tissue and skeletal muscle. Primary culture of myoblasts was established.ResultsAs expected, exercise training improved aerobic capacity and decreased fat mass. No significant change in interleukin 6, fibroblast growth factor 21, myostatin or irisin mRNA level was found in muscle after training. A 2-fold increase in apelin mRNA level was found in muscle but not in adipose tissue. No change in circulating myokine and adipokine plasma levels was observed in the resting state in response to training. Interestingly, apelin was significantly expressed and secreted in primary human myotubes. Apelin gene expression was up-regulated by cyclic AMP and calcium unlike the other myokines investigated. Importantly, muscle apelin mRNA levels were positively related to whole-body insulin sensitivity.Conclusion
Collectively, our data show that exercise training up-regulates muscle apelin expression in obese subjects. Apelin expression is induced by exercise signalling pathways and secreted in vitro in human primary myotubes, and may behave as a novel exercise-regulated myokine with autocrine/paracrine action.International Journal of Obesity accepted article preview online, 27 August 2013. doi:10.1038/ijo.2013.158.

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    • "There were no objective measures of physical activity available, which would have been an interesting addition to the present analysis. It should be noted that the initial finding that irisin is regulated by exercise in humans has only been reproduced in selective cohorts (Aydin et al., 2013; Boström et al., 2012; Huh et al., 2012; Kraemer, Shockett, Webb, Shah, & Castracane, 2014; Lecker et al., 2012; Norheim et al., 2014; Timmons, Baar, Davidsen, & Atherton, 2012), but not in all (Aydin et al., 2013; Besse-Patin et al., 2014; Hecksteden et al., 2013; Hofmann et al., 2014; Huh et al., 2012; Kraemer et al., 2014; Moraes et al., 2013; Norheim et al., 2014; Pekkala et al., 2013; Phillips et al., 2012; Raschke et al., 2013; Timmons et al., 2005). We did not include measures of other known appetitive hormones such as ghrelin, leptin or adiponectin as our primary focus was the association between ad libitum food intake and irisin. "
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    ABSTRACT: The relationship between food intake and irisin concentrations in humans is unclear. To determine whether the previous day's intake impacts fasting plasma irisin concentrations, or whether fasting irisin concentrations associate with subsequent ad libitum food intake. Sixty-six nondiabetic adults (42 men) were admitted for a study of the determinants of energy intake. After 6 days of a weight maintaining diet, ad libitum energy intake over 3 days was assessed using a vending machine paradigm. Fasting plasma irisin concentrations were measured on the morning of the second day of the vending period. There were no correlations between irisin and demographic or anthropometric parameters. On day 1, subjects consumed 144±52% of weight maintaining energy needs. Every additional 500 kcal consumed on day 1 associated with a 3.4% lower irisin concentration the following morning (95% CI -6.2, -0.4%, p = 0.01; adjusted for age, sex and race). If energy intake was expressed as a percentage of weight maintaining energy needs, every 10% increase associated with a 1.9% lower irisin concentration (95% CI -3.7, -0.1%; adjusted p = 0.02). A 100 kcal increase in carbohydrate or fat consumption associated with a 1.3% (95% CI -2.5, -0.1%, p = 0.01) and a 0.6% (95% CI -1.1, -0.0%, p = 0.02) lower irisin concentration, respectively. There was no association between fasting irisin concentrations and subsequent energy intake on day 2 (r = 0.19, p = 0.1). Higher ad libitum 24h energy intake was associated with lower fasting irisin concentrations the following morning, but fasting irisin concentrations did not predict subsequent energy intake. The decrease in irisin concentrations with increased energy intake is consistent with the detrimental metabolic effects of overeating. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Mar 2015 · Appetite
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    ABSTRACT: Objective Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain. Materials/Methods Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and were re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2). Results After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039). Conclusions Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.
    No preview · Article · Dec 2013 · Metabolism
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    ABSTRACT: The recently described myokine, irisin is cleaved from fibronectin type III domain containing protein 5 (FNDC5) and has been proposed to be secreted upon exercise to promote the browning of beige fat cells in white adipose tissue that results in enhanced thermogenesis and increased energy expenditure. The initial studies suggested irisin as a treatment option for obesity and associated diseases such as type 2 diabetes mellitus and stimulated further research. However, the results of subsequent studies investigating the regulation of irisin by different types of exercise are partly conflicting and effects were only shown in highly selective patient populations so far. Moreover, other parameters like body weight or fat free mass were shown to influence irisin adding more complexity to the mechanisms regulating this hormone. The present review will describe the discovery of irisin, its potential role in adipose tissue-mediated thermogenesis, its regulation by exercise and lastly, discuss current controversies and highlight gaps of knowledge to be filled by future studies.
    No preview · Article · Jan 2014 · Peptides
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