Oncotarget

Research Papers:

Regulation of malonyl-CoA-acyl carrier protein transacylase network in umbilical cord blood affected by intrauterine hyperglycemia

Yong Zhang, Jianping Ye and Jianxia Fan _

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Oncotarget. 2017; 8:75254-75263. https://doi.org/10.18632/oncotarget.20766

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Abstract

Yong Zhang1,2, Jianping Ye3 and Jianxia Fan1

1International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China

2Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

3Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA

Correspondence to:

Jianxia Fan, email: fanjianxia122@126.com

Yong Zhang, email: yzhang415@163.com

Keywords: pregnancy, MCAT, offspring, gestational diabetes, umbilical cord blood

Received: March 15, 2017    Accepted: July 30, 2017    Published: September 08, 2017

ABSTRACT

Background: Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved in the insulin resistance in offspring are still unclear. Mitochondrial dysfunction is related with insulin resistance. In mitochondria, malonyl-CoA-acyl carrier protein transacylase (MCAT) is the key enzyme of mitochondrial fatty acid synthesis and is estimated to contribute to insulin resistance. In this study, we aimed to examine the role of MCAT and its network in the umbilical cord blood in GDM-induced offspring insulin resistance.

Methods: We isolated lymphocytes from umbilical cord vein blood in 6 GDM patients and 6 controls and examined the differences of RNA by RNA sequencing. qRT-PCR and western blot were used to measure mRNA and protein changes. Bisulfite genomic sequencing PCR was applied to detect DNA methylation.

Results: We found more than 400 genes were differentially regulated in the lymphocytes of umbilical cord blood from GDM patients and these genes were mainly enriched in immune system and endocrine system, which relate to mitochondrial dysfunction and insulin resistance. MCAT closely related with PTPN1 (Protein Tyrosine Phosphatase, Non-Receptor Type1) and STAT5A (Signal Transducer And Activator of Transcription 5A), which were all increased in umbilical cord blood from GDM patients. Increase in MCAT may be due to decreased MCAT DNA methylation.

Conclusion: MCAT and its network with PTPN1, STAT5A are regulated in umbilical cord blood affected by maternal intrauterine hyperglycemia.


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