Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus

Ning, Hui; Hong, Tao; Weng, Zhanping; Zhao, Xianxian

doi:10.1007/s00592-016-0867-8

Cited by 34 publications

(38 citation statements)

References 61 publications

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“…FABP4 promoter has a binding site for insulin, fatty acids, and hypoxia-inducible factor [60,61], and these are all increased in GDM conditions [45,62,63], possibly contributing to FABP3 and FABP4 promoter activation and upregulation. Consistent with our findings, increased placental FABP3 and FABP4 expression and a strong correlation of circulatory FABP4 levels with GDM have been reported [27,64].…”

Section: Discussionsupporting

confidence: 93%

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

et al. 2020

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Gestational diabetes mellitus (GDM) results in reduced docosahexaenoic acid (DHA) transfer to the fetus, likely due to placental dysfunction. Sirtuin-1 (SIRT1) is a nutrient sensor and regulator of lipid metabolism. This study investigated whether the high glucose and insulin condition of GDM regulates DHA transfer and expression of fatty acid transporters and if this effect is related to SIRT1 expression and function. Syncytialized primary human trophoblasts were treated with and without glucose (25 mmol/L) and insulin (10−7 mol/L) for 72 h to mimic the insulin-resistance conditions of GDM pregnancies. In control conditions, DHA transfer across trophoblasts increased in a time- and dose-dependent manner. Exposure to GDM conditions significantly decreased DHA transfer, but increased triglyceride accumulation and fatty acid transporter expression (CD36, FABP3, and FABP4). GDM conditions significantly suppressed SIRT1 mRNA and protein expression. The SIRT1 inhibitor decreased DHA transfer across control trophoblasts, and recombinant SIRT1 and SIRT1 activators restored the decreased DHA transport induced by GDM conditions. The results demonstrate a novel role of SIRT1 in the regulation of DHA transfer across trophoblasts. The suppressed SIRT1 expression and the resultant decrease in placental DHA transfer caused by high glucose and insulin levels suggest new insights of molecular mechanisms linking GDM to fetal DHA deficiency.

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Section: Discussionsupporting

confidence: 93%

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

et al. 2020

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“…Moreover, FABP4 and OC levels were elevated in both second and third trimester, which indicated that occasion of measurement may not influence the relationship of FABP4 and OC concentrations with GDM. Consequently, it was assumed that GDM was described as a rise of FABP4 and OC, in line with findings supported by Ning et al [52] and Abell et al [53]. Moreover, the measurement method possibly was a source of heterogeneity across the seven studies, but subgroup analysis stratified by the measurement method showed a discrepant result when the OC levels were detected by IRMA.…”

Section: Discussionsupporting

confidence: 61%

Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis

Sun

Zhang

et al. 2020

Lipids Health Dis

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Objective: Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM. Methods: Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed. Results: Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = − 0.11, 95% CI-0.61-0.38, 95% PI-1.63-1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28-3.69, 95% PI 0.28-5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31-1.05, 95% PI-0.48-1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups. Conclusions: Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.

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“…FABP4, also known as adipocyte FABP (A-FABP), is a member of a lipid-binding protein super-family. FABP4 is highly expressed in adipocytes and consists of about 1% of all soluble proteins in the adipose tissue [19]. Expression of FABP4 is highly induced during adipocyte differentiation and transcriptionally controlled by peroxisome proliferator-activated receptor γ (PPARγ) agonists, unsaturated long-chain fatty acids, dexamethasone, and insulin-like growth factor 1 [19,20,21].…”

Section: Introductionmentioning

confidence: 99%

“…FABP4 is highly expressed in adipocytes and consists of about 1% of all soluble proteins in the adipose tissue [19]. Expression of FABP4 is highly induced during adipocyte differentiation and transcriptionally controlled by peroxisome proliferator-activated receptor γ (PPARγ) agonists, unsaturated long-chain fatty acids, dexamethasone, and insulin-like growth factor 1 [19,20,21]. FABP4 is also detected in a subset of the endothelial cells and macrophages, where it increases accumulation of cholesterol ester and foam cell formation via inhibition of the PPARγ-liver X receptor α (LXRα)-ATP-binding cassette A1 (ABCA1) pathway and induces inflammatory responses through activation of the IKK-NF-κB and JNK-AP-1 pathways [21].…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid-Binding Protein 4—An “Inauspicious” Adipokine—In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus

Kimber-Trojnar

Patro-Małysza

Trojnar

et al. 2018

JCM

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The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

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Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus

Abstract: These results suggest that serum FABP4 may potentially serve as a novel biomarker for the prediction of GDM.

Cited by 34 publications

References 61 publications

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis

Fatty Acid-Binding Protein 4—An “Inauspicious” Adipokine—In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus

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