Elsevier

Metabolism

Volume 73, August 2017, Pages 100-108
Metabolism

Clinical Science
Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents

https://doi.org/10.1016/j.metabol.2017.05.007Get rights and content

Abstract

Context

Irisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism.

Objective

We studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels.

Materials and Methods

Data were obtained from the Korean Children–Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12–15 years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit.

Results

Mean body mass index (BMI) was 19.4 kg/m2 in normal-weight adolescents and 31.4 kg/m2 in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p  0.006). Of these, increased body fat mass [standardized (Std) ß, 0.23; p < 0.0001], LDL-C (Std ß, 0.14; p = 0.0005) and fasting glucose (Std ß, 0.08; p = 0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19–3.87] and MetS (OR, 2.0; CI, 1.15–3.47). Furthermore, irisin and branched-chain amino acids were positively associated (p < 4 × 10 4 for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys (p = 0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents (p = 0.0388). The relationship between physical activity and irisin levels was not observed in obese adolescents.

Conclusions

Elevated serum irisin was independently associated with the risk of obesity and positively correlated with unhealthy metabolic parameters and metabolites. Moreover, irisin levels were higher in active versus sedentary adolescents in the normal-weight group, but not in the obese group. Our findings suggest that irisin plays an important role in metabolic disorders and may be affected by physiopathological status.

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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