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The adipokine FABP4 is a key regulator of neonatal glucose homeostasis
Idit Ron, … , Itai M. Pessach, Amir Tirosh
Idit Ron, … , Itai M. Pessach, Amir Tirosh
Published October 22, 2021
Citation Information: JCI Insight. 2021;6(20):e138288. https://doi.org/10.1172/jci.insight.138288.
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Research Article Endocrinology Metabolism

The adipokine FABP4 is a key regulator of neonatal glucose homeostasis

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Abstract

During pregnancy, fetal glucose production is suppressed, with rapid activation immediately postpartum. Fatty acid–binding protein 4 (FABP4) was recently demonstrated as a regulator of hepatic glucose production and systemic metabolism in animal models. Here, we studied the role of FABP4 in regulating neonatal glucose hemostasis. 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 level of FABP4 was higher in the fetal versus maternal circulation, with a further rise in neonates after birth of approximately 3-fold. Neonatal FABP4 inversely correlated with blood glucose, with an approximately 10-fold increase of FABP4 in hypoglycemic neonates. When studied in mice, blood glucose of 12-hour-old WT, Fabp4–/+, and Fabp4–/– littermate mice was 59 ± 13 mg/dL, 50 ± 11 mg/dL, and 43 ± 11 mg/dL, respectively. Similar to our observations in humans, FABP4 levels in WT mouse neonates were approximately 8-fold higher compared with those in adult mice. RNA sequencing of the neonatal liver suggested altered expression of multiple glucagon-regulated pathways in Fabp4–/– mice. Indeed, Fabp4–/– liver glycogen was inappropriately intact, despite a marked hypoglycemia, with rapid restoration of normoglycemia upon injection of recombinant FABP4. Our data suggest an important biological role for the adipokine FABP4 in the orchestrated regulation of postnatal glucose metabolism.

Authors

Idit Ron, Reut Kassif Lerner, Moran Rathaus, Rinat Livne, Sophie Ron, Ehud Barhod, Rina Hemi, Amit Tirosh, Tzipora Strauss, Keren Ofir, Ido Goldstein, Itai M. Pessach, Amir Tirosh

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Figure 1

Maternal, fetal, and neonatal FABP4 circulating levels.

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Maternal, fetal, and neonatal FABP4 circulating levels.
Serum samples we...
Serum samples were collected from 22 normoglycemic pregnant women and 18 women with GDM. All samples were collected at term, immediately before delivery. (A) FABP4 serum concentrations were determined using an ELISA assay and were correlated to BMI. (B) Comparison between FABP4 levels in normoglycemic pregnant woman (n = 22) and women with GDMA1 (n = 10) or GDMA2 (n = 8). (C) Serum samples, collected from umbilical artery (n = 22) and vein (n = 22) immediately after delivery of normoglycemic women were analyzed for FABP4 levels and compared with (normoglycemic) maternal (n = 22) concentrations. (D) Serum samples collected from neonates within the first few hours of life (n = 24) were analyzed for FABP4 levels and compared with fetal (n = 22) and maternal levels (n = 22). (E) FABP4 levels stratified to neonates who were small (SGA) (n = 7), appropriate (AGA) (n = 48), and large (LGA) (n = 5) for gestational age. (F) Birth weight of 40 neonates was correlated to FABP4 serum concentrations. Statistical analysis includes Spearman’s correlation test (A and F) and 1-way ANOVA (B–E). Data are shown as the mean ± SEM. *P < 0.05.

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