Our prospective study shows that cord blood irisin levels are positively correlated with birth weight in term infants and the levels are decreased in SGA compared to AGA infant. Today number of the studies about serum levels of irisin in term infants with SGA and AGA is limited. We believe that it would provide contribution to the literature.
Because the underlying mechanisms and the relationship between SGA infants who have lower muscle and BAT tissue, impaired glucose tolerance still remain unclear. Also irisin is considered as a potential biomarker for obesity and metabolic syndrome.
Studies from the literature have usually emphasized the excess nutrition during early life include resetting of hypothalamic energy sensing and appetite regulation, altered adipose tissue insulin sensitivity and impaired BAT function (Stettler et al. 2002; Druet et al. 2012; Soto et al. 2003; Shalini et al. 2013). Also in animal models it has been demonstrated that in utero malnutrition affects pancreatic β-cell development leading to impaired β-cell function later in life (Garofano et al. 1997, 1999; Limesand et al. 2005). However this studies have shown that excess nutrition is a risk factor for obesity and insulin resistance not only in SGA infants but also in AGA neonates. For example; in a large multicentre randomized trial of protein supplementation of infant formula milk in 1138 infants, those receiving the higher-protein milk formula (albeit containing less protein than contemporary commercial formula milks) were of increased bodyweight at 2 years of age (Koletzko et al. 2009).
Today, different physiopathological factors are more commonly mentioned in explanation of impaired carbohydrate metabolism which is seen more frequently in SGA cases and the studies have focused particularly on irisin that is seen as a potential biomarker for development of obesity and metabolic syndrome. In the most recent study, Joung et al. found plasma irisin levels were positively correlated with gestational age (r = 0.21, p < 0.001), and birth weight Z-score (r = 0.18, p < 0.001) (Joung et al. 2015). In that study, there was a significant difference between the gestational age of newborns (26–41 GW), whereas in our study, the mean gestational week was found as GW = 38.8 ± 0.4. Though it is stated in the same publication that, no significant correlation was found between the gestational week and irisin level in multivariate analysis (β = 0.005, p = 0.43), this result may be attributed to that, 257 cases were AGA and 60 were SGA newborns, because there is a numerically significant difference between the groups. In order to eliminate this difference, we equated the number of subjects in both groups (AGA = 34, SGA = 34). Again in the same report, no statistically significant difference was found between GW and irisin in contrary to the hypothesis of body mass index and BAT are correlated with irisine, which is emphasized in the same study (SGA, AGA, LGA median 55.38, 64.41, 68.70 ng/ml; respectively). Because BMI and BAT of premature infants are low, independently from term newborns being SGA, AGA or LGA. In our study, in order to eliminate this difference all newborns enrolled were chosen from term infants (median 38.8 ± 0.4 GW). Furthermore, it is reported in the mentioned study that, singleton infants of mothers with preeclampsia had lower cord blood irisin levels compared to infants of mothers with our preeclampsia. Unlike that study, pregnants with the conditions that could affect irisin level such as maternal preaclampsia, gestational diabetes, asthma, chronic disease or a history of drug use were excluded from our study.
In addition our study, mothers with gestational diabetes, hypertension, asthma, chronic disease, use of drug or a history of smoking exposure were not included, because Garces et al. recently reported that circulating irisin levels in pregnant women with preeclampsia were lower compared to women with healthy pregnancies in the third trimester (Garces et al. 2014). Additionally, recent reports of irisin in relation to gestational diabetes mellitus (GDM) have shown controversial results between maternal circulating irisin levels and GDM (Yuksel et al. 2014; Ebert et al. 2014).
Studies in the literature conducted with healthy adults found higher irisin levels unlike our study (Park et al., n = 107 ng/ml) (Park et al. 2013). Whereas in the present study we found significantly lower irisin levels in infants compared to those in adults [median 30 (32 ± 13) ng/ml]. This difference might be attributable to the smaller muscular mass in neonates. Because in human tissues, the distribution of FNDC5 expression was strongly increased in muscle in comparison with adipose tissue, similar to the findings described in mice (Huh et al. 2012). Huh et al. found, age-related muscle loss correlated to decreased circulating irisin concentration, muscle mass being the main predictor of this in humans. Furthermore after bariatric surgery-induced weight loss, circulating irisin levels as well as muscle FNDC5 gene expression were significantly down-regulated (Huh et al. 2012).
I think that, likewise the study by Joung et al., lower cord irisin levels found SGA infants in our study might be influenced by the smaller muscular mass as well as lower BAT (Joung et al. 2015). Because, José et al. found a positive association of FNDC5 gene expression with BAT markers (PRDM16 and UCP1), lipogenic (FASN and ACC), and the expression of insulin-pathway related genes (GLUT4 and IRS1), mitochondrial (MTCO3 and PGC1), and alternative macrophage markers (IL-10 and CD206) (José et al. 2013). Also van Marken Lichtenbelt et al. showed that the amount of BAT was significantly decreased in association with obesity, with a negative linear relationship between BAT, BMI, and percent body fat (van Marken Lichtenbelt et al. 2009).
Based on all these studies and the present study; I have thought that irisin which is recently rather emphasized for its association with insulin resistance and obesity and released by muscle tissue, regulating glucose homeostasis by influencing the BAT might be a physiopathological factor in explanation of the impaired carbohydrate metabolism which is more common in SGA infants. Because both muscular mass and BAT are low in SGA infants.