Clinical ScienceAssociation of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents
Introduction
Obesity, characterized by excess adipose tissue and associated with serious co-morbidities including metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM), has rapidly become a worldwide epidemic [1], [2]. Although the etiology of obesity is complex, the key factor is long-term dysregulation of energy balance, such as increased energy intake and/or reduced energy expenditure [2]. Thus, it is crucial to understand the regulation of energy homeostasis to prevent obesity and its complications.
Irisin is a newly identified novel myokine that regulates energy metabolism. Previous studies have shown that exercise stimulates peroxisome proliferator-activated receptor-γ coactivator-1α, which in turn upregulates the expression of fibronectin type III domain containing 5 (FNDC5). Irisin is cleaved from FNDC5 in skeletal muscle cells and then increases thermogenesis, which improves glucose homeostasis [3], [4]. Furthermore, irisin was suggested to be involved in the pathogenesis of various complications of obesity, including dyslipidemia, T2DM, and MetS [5], [6], [7], [8].
The effect of exercise training on circulating irisin and the role of irisin in glucose/energy homeostasis in humans are controversial. For example, several previous studies have shown increases in irisin after exercise or lifestyle interventions [3], [9], [10], [11], whereas others failed to find an increase in the hormone [12], [13], [14]. Furthermore, several studies found a positive association of irisin levels with body mass index (BMI), insulin resistance (IR), and MetS [5], [15], [16], [17], whereas others reported negative correlations [18], [19], [20]. Although these contradictory findings raise concerns about the association of irisin with physical activity and metabolic parameters, irisin has not been widely studied in children and adolescents. Only a few investigations using small samples of Western children have examined the relationships between circulating irisin and anthropometric measures [21], [22], [23], body composition [23], physical activity [22], puberty, [21] and biochemical parameters [21], [22], [23], [24]. Moreover, no previous study has assessed the association between circulating irisin levels and metabolites. Therefore, we investigated the relationship of circulating irisin with metabolic parameters and metabolites and examined the effects of physical activity, obesity, and MetS on irisin levels in Korean adolescents.
Section snippets
Study Participants
Data were obtained from the Korean Children–Adolescents Study, conducted by the Korea National Institute of Health. The overall objective of this cohort study was to identify early risk factors for obesity and associated metabolic disease in Korean children and adolescents. The study subjects consisted of 647 non-diabetic adolescents, aged 12 to 15 years and with available blood samples, from Seoul and Gyunggi Provinces between 2011 and 2013. After excluding subjects who did not respond to the
Subject Characteristics
The general characteristics of the subjects are shown in Table 1. A total of 370 normal-weight and 248 obese adolescents between the ages of 12 and 15 years were included in the study. The sex distribution was not significantly different between groups. The adiposity indices (BMI, waist circumference, percent body fat, fat mass, fat-free mass, and fat mass to fat-free mass ratio) and clinical biomarkers (lipid profile [TC, LDL-C, and TG], glycemic profile [fasting glucose, insulin, and HOMA-IR],
Discussion
We found that elevated serum irisin levels were positively correlated with an unhealthy metabolic profile, including adiposity indices and lipid and glycemic parameters, in Korean adolescents. Furthermore, serum irisin levels were independently associated with obesity and body fat mass was the primary determinant of high irisin levels. Our findings suggest that serum irisin levels are affected by body fat mass and associated with the risk of obesity.
Although the regulation of irisin in obese
Conclusions
We found a positive relationship between serum irisin levels and markers of adiposity, lipid, and glucose metabolism, which are related to obesity and MetS, in Korean adolescents. Moreover, we found a positive association between irisin and BCAA and related metabolites in obese adolescents. Additionally, adolescents in the normal-weight group who regularly engaged in physical activity had higher levels of irisin than did sedentary adolescents. This relationship was not observed in obese
Author Contributions
H.B.J., H.J.L., and K.H.P designed the study; H.B.J. analyzed the data and wrote the manuscript; H.J.L. and K.H.P reviewed the manuscript; K.H.P. and J.H.K. collected data; H.B.J., H.J.L., H.J.K. and S.I.P. interpreted the data.
Funding
This work was supported by intramural grants from the Korea National Institute of Health and Korea Center for Disease Control and Prevention [project number: 2017-NG64003-00].
Disclosure Statement
The authors have nothing to disclose.
Acknowledgments
We thank all of the participating adolescents and their parents.
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