The Adipokine FABP4 – A Key Regulator of Neonatal Glucose Homeostasis
2Department of Pediatrics, the Edmond and Lily Safra Children's Hospital, Sheba Medical Center
3Department of Neonatology, the Edmond and Lily Safra Children's Hospital, Sheba Medical Center
4Department of Pediatric Intensive Care, the Edmond and Lily Safra Children's Hospita, Sheba Medical Center
5Department of Obstetrics and Gynecology, Sheba Medical Center
6Endocrinology laboratories, Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center
7Endocrine Cancer Genomics Center, Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center
8Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem
9Sackler School of Medicine, Tel-Aviv University
During pregnancy, fetal glucose production is suppressed, with rapid activation immediately post-partum. Fatty acid-binding protein 4 (FABP4) was recently demonstrated as a regulator of hepatic glucose production and systemic metabolism in animal models.
Aims:
To evaluate FABP4’s role in regulating neonatal glucose hemostasis.
Methods:
Serum samples were collected from pregnant women with normoglycemia or gestational diabetes at term, from the umbilical circulation, and from the newborns within 6 hours of life. The direct impact of FABP4 on glucose homeostasis was studied by injection of recombinant FABP4 to Fabp4-knockout (Fabp4-/-) neonates. Mice neonatal liver were also subjected to transcriptome analysis.
Results:
FABP4 level was higher in the fetal vs. maternal circulation with a further rise in neonates after birth by ~3-fold. Neonatal FABP4 inversely correlated with blood glucose with ~10-fold increase in hypoglycemic neonates. When studied in mice, blood glucose of 12hr-old wild-type, Fabp4-/+ and Fabp4-/- littermate mice was 59±13 ng/dL, 50±11 mg/dL and 43±11 mg/dL, respectively (p<0.05). Similar to our observations in humans, FABP4 levels in wild-type mice neonates was ~8-fold higher compared to adult mice. RNA-Seq of neonatal liver suggested altered expression of multiple glucagon-regulated pathways in Fabp4-/- mice. Indeed, Fabp4-/- liver glycogen was inappropriately intact, despite a significant hypoglycemia, with rapid restoration of normoglycemia upon injection of recombinant FABP4.
Conclusions:
Our results highlight the importance of FABP4 as a significant factor in regulating post-natal systemic glucose metabolism, as part of the orchestrated hormonal and metabolic adaptive response to maintain glucose homeostasis in the immediate post-natal period.
