The adipokine FABP4 as a regulator of neonatal glucose homeostasis

During normal pregnancy, fetal hepatic gluconeogenesis (GNG) is absent and is evident only soon after birth with a rapid increase in the expression of phosphoenolpyruvate carboxykinase (PEPCK). PEPCK expression is regulated by the adipokine fatty acid-binding protein 4 (FABP4) which plays key roles in systemic metabolism and in promoting GNG. We hypothesized that FABP4 may play an important role in neonatal glucose homeostasis by regulating the GNG ‘switch-on’ immediately after birth. Therefore we studied the dynamics of serum FABP4 from maternal, fetal and neonatal samples. Serum samples were collected from 47 pregnant women at term immediately before delivery (51% with gestational diabetes, GDM), from the umbilical artery and vein after birth and from the newborns within the first few hours of life. In the fetal circulation, FABP4 level was significantly higher than in non-diabetic mothers (23.3±15.3 and 23.6±15.2 ng/mL for umbilical artery and vein, respectively vs. 15.2±7.6 ng/mL in normoglycemic women, p<0.05 for both). Neonatal FABP4 after birth increased ~3-fold, (65.2±37.5 ng/mL,p<0.001). Moreover, neonatal FABP4 level inversely correlated with blood glucose with marked increase in hypoglycemic neonates. We next assessed glucose levels in FABP4-knockout (FABP4-KO) mice within 24 hours of birth, confirming a significantly lower blood glucose in the absence of FABP4 (60±11, 54±8 and 48±10 for wild-type, heterozygotes and FABP4-KO respectively, p<0.03), confirming its key role in maintaining post-natal glycemia. Our data suggest that FABP4 is a key adipokine regulating glucose homeostasis in newborns.