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Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts.

ABSTRACT: Maternal obesity, gestational diabetes (GDM), or type 2 diabetes (T2DM) is associated with altered lipid metabolism and fetal overgrowth.The objective of the study was to test the hypothesis that hyperlipidemia and hyperinsulinemia regulate lipid content and expression of lipid-trafficking proteins in human placental trophoblasts.Pregnant women were prospectively enrolled for clinical specimens collection, and cultured human trophoblasts were used for experiments.This was a translational study conducted at an academic biomedical research center.Normal weight, obese, or obese with gestational diabetes or type 2 diabetes pregnant women (n = 10 in each group) undergoing scheduled cesarean delivery at term were enrolled.Cultured primary human trophoblasts, exposed to insulin (10 nM) and/or fatty acids mix (1200 ?M) in the absence or presence of an fatty acid binding protein 4 (FABP4) inhibitor or after small interfering RNA-mediated knockdown of FABP4.Serum lipid levels were analyzed in the maternal venous and fetal cord blood. Placental biopsies and cultured trophoblasts were analyzed for FABP expression and lipid accumulation.Obese diabetic women and their fetuses had elevated serum triglyceride levels. Nonesterified fatty acids were elevated and triglycerides were reduced in placental villi from obese diabetic women, and this was accompanied by a 2.6-fold increase in FABP4 expression (P < 0.05). In primary human trophoblasts, fatty acids markedly increased the expression of FABP4 (20- to 40-fold, P < 0.05) and cellular triglyceride content (4-fold, P < 0.05), and this effect was attenuated by small interfering RNA-mediated knockdown of FABP4 or the selective FABP4 inhibitor BMS309403.Hyperlipidemia alters lipid content and increases the expression of FABP4 in trophoblasts. The reduced triglyceride content after FABP4 inhibition suggests that FABP4 is essential for trophoblast lipid accumulation.

SUBMITTER: Scifres CM

PROVIDER: S-EPMC3135200 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts.

Scifres Christina M CM Chen Baosheng B Nelson D Michael DM Sadovsky Yoel Y

The Journal of clinical endocrinology and metabolism 20110427 7

<h4>Context</h4>Maternal obesity, gestational diabetes (GDM), or type 2 diabetes (T2DM) is associated with altered lipid metabolism and fetal overgrowth.<h4>Objective</h4>The objective of the study was to test the hypothesis that hyperlipidemia and hyperinsulinemia regulate lipid content and expression of lipid-trafficking proteins in human placental trophoblasts.<h4>Study design</h4>Pregnant women were prospectively enrolled for clinical specimens collection, and cultured human trophoblasts wer ...[more]

PMID: 21525163

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Project description:Methods: We performed mRNA sequence analysis by deep sequencing, in triplicate, using Illumina HiSeq to assess the impact of PHLPP1 knockdown in regulating gene expression in RAW 264.7 cells treated with/without OxLDL. The transcriptome libraries were constructed using the NEB adapters and were sequenced on at 150 nucleotide read length using the paired-end chemistry. The raw reads were subjected to Adapter and low-quality reads removal by Trimmomatic -0.36v. The raw reads were subjected to contamination [structural RNA / low complexity sequences] removal by mapping with bowtie 2-2.2.1. The decontaminated data set was mapped to the mouse genome. Reads mapping to gene list were counted using feature count module of sub reads package. The read counts were normalized in DESeq2-3.5, and subject to differential expression analysis. Differentially expressed genes were selected based on log2-ratio change with p-value <0.05 (Student’s t-test, unpaired). Hierarchical clustering was performed with the programs Cluster (uncentered correlation; average linkage clustering) and Treeview. Results: To gain a deeper understanding of the role of PHLPP1 in lipid metabolism in macrophages, we performed mRNA Seq analysis to assess the gene expression changes in a mouse macrophage cell line. The experiment has been carried out in triplicates. Alignment of the reads showed 97% alignment to the reference mouse genome. Identification of the differentially expressed genes were then carried out by DESeq2 version 1.2.10 with stringent criteria (FDR <0.05% with 2 fold up and down regulation) which reveals in control treated vs. control (121-down, 396-Up), Test vs. Control - (326-down, 569 Up) and Test treated vs. control treated (1314-down, 1328 up) of DEG to be altered in expression respectively. Inference: RNA-seq analysis revealed that PHLPP1 knockdown parallel with OxLDL treatment resulted in diminished expression profile of cholesterol biosynthesis and lipid metabolism genes.

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Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts.

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Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts.

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