Cord blood irisin at the extremes of fetal growth

Abstract

Background/aims: Irisin, a novel myokine with antiobesity properties, drives brown-fat-like conversion of white adipose tissue, thus increasing energy expenditure and improving glucose tolerance. We aimed to investigate circulating irisin concentrations in large-for-gestational-age (LGA) and intrauterine-growth-restricted (IUGR) fetuses, both associated with metabolic dysregulation and long-term susceptibility to obesity and metabolic syndrome development.

Methods: Plasma irisin and insulin concentrations were determined by ELISA and IRMA, respectively, in 80 mixed arteriovenous cord blood samples from LGA (n=30), IUGR (n=30) and appropriate-for-gestational-age (AGA, n=20) singleton full-term pregnancies. Fetuses were classified as LGA, IUGR or AGA, based on customized birth-weight standards adjusted for significant determinants of fetal growth.

Results: Fetal irisin concentrations were lower in IUGR cases than AGA controls (p=0.031). Cord blood irisin concentrations were similar in LGA and AGA groups and positively correlated with birth-weight, as well as customized centiles (r=0.245, p=0.029 and r=0.247, p=0.027, respectively). Insulin concentrations were higher in LGA, compared to AGA fetuses (p=0.036). In the LGA group, fetal irisin concentrations positively correlated with fetal insulin concentrations (r=0.374, p=0.042).

Conclusions: Impaired skeletal muscle metabolism in IUGR fetuses may account for their irisin deficiency, which may be part of the fetal programming process, leading to increased susceptibility to later metabolic syndrome development. Furthermore, irisin down-regulation may predispose IUGR infants to hypothermia at birth, by inducing less "browning" of their adipose tissue and consequently less non-shivering thermogenesis. Irisin upregulation with increasing birth-weight may contribute to a slower fat gain during early infancy ("catch-down"), by promoting higher total energy expenditure. The positive correlation between irisin and insulin in the LGA group may reflect a counterbalance of the documented hyperinsulinemia, which is partly responsible for the excessive fat deposition in the LGA fetus.

Keywords: Fetal macrosomia; Fetus; Insulin resistance; Intrauterine growth restriction; Irisin.