Feifei Ma

Cystathionine beta-synthase 844ins68 polymorphism is unrelated to susceptibility to neural tube defects.

OBJECTIVE Cystathionine beta-synthase (CBS) 844ins68 polymorphism has been implicated in the development of neural tube defects (NTDs). However, the results of different studies are inconsistent. Thus, we conducted a meta-analysis to further investigate this association. METHODS Published studies were retrieved from PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data. Studies that evaluated the association between CBS 844ins68 polymorphism and NTD risk among mothers, children, or fathers were included. The pooled odds ratios with 95% confidence interval were calculated using a fixed effects model or a random effects model. RESULTS A total of eight studies on mothers (641 cases and 1145 controls), eight studies on children (852 cases and 1912 controls), and five studies (263 cases and 1562 controls) on fathers were included. The meta-analysis revealed no significant association between CBS 844ins68 polymorphism and NTD risk among mothers, children, and fathers under either genetic model. CONCLUSION The present meta-analysis indicates that CBS 844ins68 polymorphism is not a good predictor of risk for NTDs.

Association between Long Interspersed Nuclear Element-1 Methylation and Relative Telomere Length in Wilms Tumor

Background:DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT. Methods:We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results:LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2′-deoxycytidine compared with untreated WT cell line. Conclusion:These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.

miR-206-3p Inhibits 3T3-L1 Cell Adipogenesis via the c-Met/PI3K/Akt Pathway

MicroRNAs (miRNAs) are important post-transcriptional regulators during adipocyte adipogenesis. MiR-206-3p, a tissue-specific miRNA, is absent in white adipocytes. In this study, we examined the roles of mmu-miR-206-3p in the adipogenic differentiation of 3T3-L1 preadipocytes. The miR-206-3p expression has shown an apparent decreasing trend after induction, and sustained low expression throughout the differentiation of 3T3-L1 cells. miR-206-3p blocked the adipogenic differentiation of 3T3-L1 cells by attenuating c-Met expression; the inhibition effect of miR-206 to the adipogenic differentiation can be counteracted by restoring c-Met expression. In addition, miR-206-3p decreased the phosphorylation of Akt, which is the downstream effector of c-Met in the PI3K/Akt signaling pathway. These data indicate that miR-206-3p inhibits adipocyte adipogenesis through silencing c-Met and subsequently inactivating the PI3K/Akt signaling pathway.

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement

Background/Aims: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart. Methods: Heart samples were collected from mice fed with standard diet (SD), high-fat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups. Results: The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajb1, Egr2, Hba-a1, Il1β, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF. Conclusions: Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity.

Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice

Folic acid (FA) supplementation may protect from obesity and insulin resistance, the effects and mechanism of FA on chronic high-fat-diet-induced obesity-related metabolic disorders are not well elucidated. We adopted a genome-wide approach to directly examine whether FA supplementation affects the DNA methylation profile of mouse adipose tissue and identify the functional consequences of these changes. Mice were fed a high-fat diet (HFD), normal diet (ND) or an HFD supplemented with folic acid (20 μg/ml in drinking water) for 10 weeks, epididymal fat was harvested, and genome-wide DNA methylation analyses were performed using methylated DNA immunoprecipitation sequencing (MeDIP-seq). Mice exposed to the HFD expanded their adipose mass, which was accompanied by a significant increase in circulating glucose and insulin levels. FA supplementation reduced the fat mass and serum glucose levels and improved insulin resistance in HFD-fed mice. MeDIP-seq revealed distribution of differentially methylated regions (DMRs) throughout the adipocyte genome, with more hypermethylated regions in HFD mice. Methylome profiling identified DMRs associated with 3787 annotated genes from HFD mice in response to FA supplementation. Pathway analyses showed novel DNA methylation changes in adipose genes associated with insulin secretion, pancreatic secretion and type 2 diabetes. The differential DNA methylation corresponded to changes in the adipose tissue gene expression of Adcy3 and Rapgef4 in mice exposed to a diet containing FA. FA supplementation improved insulin resistance, decreased the fat mass, and induced DNA methylation and gene expression changes in genes associated with obesity and insulin secretion in obese mice fed a HFD.

Effects of macrophages and CXCR2 on adipogenic differentiation of bone marrow mesenchymal stem cells: CAO et al.

Macrophages and many chemokines are closely associated with the adipogenic differentiation of bone marrow mesenchymal stem cells (MSCs), but their roles in adipogenesis and the underlying mechanisms are not fully understood. Here, we first investigated the influence of macrophages on the differentiation of MSCs in vitro. We found that RAW246.7 macrophages cocultured with MSCs strongly blocked the differentiation progress and inhibited the expression of C‐X‐C motif chemokine ligand 1 (CXCL1) during adipogenesis. Coculture with MSCs mainly induced macrophages toward M2 polarization. In addition, the expression of CXCL1 and its receptor, C‐X‐C chemokine receptor type 2, CXCR2 are high during adipogenic differentiation of MSCs and not in mature adipocytes. Although CXCL1 had no effect on adipogenesis, treatment with a specific CXCR2 inhibitor, SB225002, hampered the adipogenic differentiation of MSCs. Blocking CXCR2 decreased p38 and Elk1 phosphorylation but increased the extracellular signal–regulated kinase (ERK) phosphorylation at the initial stage of adipogenesis, which suppressed the phosphorylation of p38/ERK‐Elk1 at the late stage. Inhibition of ERK had similar effects on adipogenesis and Elk1 phosphorylation. Our data suggest that MSCs interact with macrophages during adipogenic differentiation. CXCR2 regulates the adipogenic differentiation of MSCs by altering the activation of the p38/ERK‐Elk1 signaling pathway.

Characterization and predicted role of microRNA expression profiles associated with early childhood obesity

MicroRNAs (miRNAs) are implicated in the pathogenesis of obesity. The aim of the present study was to characterize the miRNA profile associated with early childhood obesity in peripheral blood mononuclear cells (PBMCs). A total of 12 children (6 obese and 6 lean controls) aged 36 months old to 48 months old were recruited. The miRNA expression profile from PBMCs was detected using the multiplexed NanoString nCounter system. Bioinformatics was employed to detect target genes and miRNA-regulated biological function. A total of 9 differentially expressed miRNAs were identified in obese children compared with lean children (P<0.05). Among the 9 miRNAs, miR-199a-3p/miR-199b-3p and miR-4454 presented at least a 1.5-fold change in expression. A total of 643 potential target genes were regulated by the three miRNAs, and 291 of the potential genes were involved in a protein interaction network. Gene ontology annotation indicated that 291 potential genes were enriched in 14 biological process annotations and 2 molecular function annotations. miRNA dysregulation may be involved in early childhood obesity.