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Integrative Biology

Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations

Abstract

Background/Objectives:

Irisin has been suggested as a novel myokine with beneficial effects in rodents. However, previous data in humans showed conflicting results regarding its association with metabolic phenotypes and regulation of secretion. Furthermore, although an association of rs726344 in FNDC5 (fibronectin type III domain containing 5) coding for irisin with insulin sensitivity was reported, the effects of genetic variation at this locus on irisin serum levels have not been investigated, so far. Therefore, we investigated circulating irisin and the associations with rs726344 in a cohort of >1000 subjects.

Subjects/Methods:

Irisin serum concentrations were measured with enzyme-linked immunosorbent assay. Associations with metabolic parameters including renal function, glucose and lipid metabolism, inflammation, as well as adipokine profiles, were assessed in regression models. Dynamic changes of serum irisin were investigated during oral glucose tolerance test (OGTT) in a subset of the cohort (n=136). rs726344 was genotyped in all subjects and analyzed for associations with serum irisin and traits of the metabolic syndrome.

Results:

Irisin was negatively associated with fat mass, fasting glucose and dyslipidemia but not with other adipokines. Moreover, irisin decreased during an OGTT in a subcohort comprising subjects with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. rs726344 was not associated with serum irisin levels or with other anthropometric and biochemical parameters.

Conclusions:

Circulating irisin levels are associated with a beneficial metabolic profile but not with other adipokines and not with rs726344 in our cohort. Our data suggest a potential favorable role of irisin in the regulation of metabolism.

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Acknowledgements

We thank all who participated in the study. Special thank goes to Beate Gutsmann for their valuable contribution to data collection and excellent technical assistance. This study was supported by grants to MF from the Deutsche Forschungsgemeinschaft (DFG, SFB 1052/1, C06), the Federal Ministry of Education and Research, Germany, FKZ: 01EO1001 (IFB AdiposityDiseases, projects K7-3, K7-9, K7-58 and K7-31) and the Deutsche Hochdruckliga eV, as well as grants to SK and TE from the Deutsche Diabetes Stiftung (DDS). Furthermore, TE was supported by the Federal Ministry of Education and Research, Germany, FKZ: 01EO1001 (IFB AdiposityDiseases, MetaRot program) and by a MSD grant (MSD Stipendium 2013 Diabetologie). Moreover, AT was supported by grants from the DFG (SFB 1052/1, C01 and SPP 1629 TO 718/2–1), from the DDG, and from the DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland).

Author contributions

TE and AT wrote the manuscript and researched the data. UW researched data and reviewed/edited the manuscript. MSch contributed to statistical analyses. PK, SK, MSch, MS and MF contributed to the discussion and reviewed/edited the manuscript.

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Correspondence to T Ebert.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Ebert, T., Kralisch, S., Wurst, U. et al. Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations. Int J Obes 40, 260–265 (2016). https://doi.org/10.1038/ijo.2015.157

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