Adipose Tissue Derived FABP4 Promotes Hepatic Glucose Production in Gestational Diabetes
2Department of Obstetrics and Gynecology, Sheba Medical Center
3Sackler School of Medicine, Tel-Aviv University
4Endocrinology Laboratories, Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center
One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which may result in significant health threats of the mother, fetus and the newborn. Fatty acid-binding protein 4 (FABP4) is an adipokine that regulates glucose homeostasis by promoting glucose production and liver insulin resistance in mice models. FABP4 levels are increased in GDM and correlates with maternal indices of insulin resistance, with a rapid decline post-partum.
Aim:
To determine the tissue origin of elevated circulating FABP4 levels in GDM and to assess its potential contribution in promoting hepatic glucose production.
Methods:
FABP4 protein and gene expression was determined in biopsies from placenta, sub-cutaneous (sWAT) and visceral (vWAT) white adipose tissues from GDM and normoglycemic pregnant woman. FABP4 differential contribution in stimulating hepatic glucose production was tested in conditioned medium before and after it’s immune clearance
Results:
We showed that FABP4 is expressed in placenta sWAT and vWAT of pregnant women at term, with a significant increase in its secretion from vWAT of women with GDM compared to normoglycemic women. Conditioned media from vWAT of pregnant women increased glucose production in isolated hepatocytes. Neutralizing FABP4 from vWAT secretome significantly suppressed glucose production. This effect was more pronounced in FABP4 derived from vWAT of pregnant women with GDM.
Conclusions:
This study provides new insights on the role of the adipose tissue-derived FABP4 in GDM, highlighting this adipokine, as a potential mediator of adipose tissue–liver axis in glucose homeostasis during pregnancy.
