The Role of the Adipokine FABP4 in the Pathophysiology of Gestational Diabetes

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, defined by hyperglycemia and insulin resistance (IR) during pregnancy. GDM is of great concern given the serious health consequences for both the mother and the offspring. Fatty acid-binding protein 4 (FABP4) is one of the most abundant proteins in mature adipocytes, and has been identified as an active adipokine modulating glucose homeostasis by promoting hepatic glucose production. Of interest, increased levels of FABP4 has been demonstrated in GDM, however its differential contribution to its pathophysiology is unclear.

Our preliminary results, in accordance with other studies, indicate significantly higher circulating levels of FABP4 in women with GDM (n=14) vs. normoglycemic pregnant women (n=55); FABP4 median 20.1 [IQR 14.6-22.6 ng/ml] vs. 10.0 [IQR: 7.8-13.9 ng/ml], p=0.01, respectively. In order to identify the source of elevated circulating levels of FABP4 in GDM we collected both subcutaneous and visceral white adipose tissue (WAT) biopsies as well as placenta samples from 17 women with GDM and 19 normoglycemic pregnant women, aged 37.5±4.6 and 36.6±5.4 years and a BMI of 29±10.1 and 24.9±6.1 kg/m², respectively. The results demonstrate that both adipose tissues and placenta express and secrete FABP4. Yet, there was a differential increase in FABP4 secretion from visceral WAT of GDM women compared to normoglycemic pregnant women, likely representing the source of elevated serum FABP4 in GDM.

This study highlights the importance of the visceral adipose tissue and FABP4 as potential contributing factors to the pathophysiology of insulin resistance in GDM.