Adipose tissue-derived FABP4 mediates glucagon-stimulated hepatic glucose production in gestational diabetes

Idit Ron, Ragad Mdah, Roni Zemet, Rakefet Yoeli Ulman, Moran Rathaus, Benny Brandt, Shali Mazaki-Tovi, Rina Hemi, Ehud Barhod, Amir Tirosh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aims: 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 mouse models. FABP4 levels are increased in GDM and correlates with maternal indices of insulin resistance, with a rapid decline post-partum. We therefore aimed to determine the tissue origin of elevated circulating FABP4 levels in GDM and to assess its potential contribution in promoting glucagon-induced hepatic glucose production. Materials and Methods: FABP4 protein and gene expression was determined in biopsies from placenta, subcutaneous (sWAT) and visceral (vWAT) white adipose tissues from GDM and normoglycaemic pregnant women. FABP4 differential contribution in glucagon-stimulated hepatic glucose production was tested in conditioned media before and after its 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 with normoglycaemic pregnant women. Neutralizing FABP4 from both normoglycaemic pregnant women and GDM vWAT secretome, resulted in a decrease in glucagon-stimulated hepatic glucose production. Conclusions: This study provides new insights into the role of adipose tissue-derived FABP4 in GDM, highlighting this adipokine, as a potential co-activator of glucagon-stimulated hepatic glucose production during pregnancy.

Original languageEnglish
Pages (from-to)3192-3201
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume25
Issue number11
DOIs
StatePublished - Nov 2023

Funding

FundersFunder number
Israeli Diabetes Foundation
Israeli Ministry of Justice
Israel Science Foundation922/17

    Keywords

    • cellular research
    • cohort study
    • glucagon
    • insulin resistance

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