Whole Transcriptome Analysis of Obese Adipose Tissue Suggests u001kfc.1 as a Potential Regulator to Glucose Homeostasis.

Linlin Yang,Wanxing Zhang,Huaibin Guo,Xing Wang,Huijuan Ma,Wei Wang

doi:10.3389/fgene.2019.01133

Linlin Yang, Wanxing Zhang + Show 4 more

Open Access

https://doi.org/10.3389/fgene.2019.01133

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Abstract

Long non-coding RNA (LncRNAs) are newly highlighted key factors controlling brown adipogenesis and development, but their regulatory effect to white adipocyte is still merely understood. Deciphering their underlying mechanism could be a novel way to discovering potential targets of obesity. Therefore, we conducted a whole transcriptome analysis in white adipose tissue from obese patients for the first time. Six obese patients and five control subjects were selected for microarray assay. Differentially expressed coding genes (DEGs), targets of lncRNAs, and alternatively spliced genes in obesity group were systematically compared in a functional framework based on a global gene regulatory network. It was demonstrated that all the three kinds of transcripts were enriched in pathways related to glucose metabolism while only DEGs showed closer proximity to neuro-endocrine-immune system. Thus, a lncRNA-regulated core network was constructed by a stepwise strategy using DEGs as seed nodes. From the core network, we identified a decreased lncRNA, uc001kfc.1, as potential cis-regulator for phosphatase and tensin homolog (PTEN) to enhance insulin sensitivity of white adipocytes in obese patients. We further validated the down-regulation of uc001kfc.1 and PTEN in an independent testing sample set enrolling 22 subjects via qRT-PCR. Although whether the decreased uc001kfc.1 correlated with low risk of diabetes deserved to be examined in an expanded cohort with long-term follow-up visit, the present study highlighted the potential of lncRNA regulating glucose homeostasis in human adipose tissue from a global perspective. With further improvement, such network-based analyzing protocol proposed in this study could be applied to interpreting function of more lncRNAs from other whole transcriptome data.

Highlights

IntroductionObesity has become a global health-threatening disease resulting from unbalanced energy intake and expenditure
Over the past decade, obesity has become a global health-threatening disease resulting from unbalanced energy intake and expenditure
It was unexpected that obesity group showed significantly lower fasting blood glucose (FBG) than control one (P = 0.019, KolmogorovSmirnov test)

Summary

Introduction

Obesity has become a global health-threatening disease resulting from unbalanced energy intake and expenditure. It was linked to adipogenesis and cell differentiation in white and brown adipocyte (Xiao et al, 2015; Xiong et al, 2018). It was found that lncRNA could dynamically regulate energy homeostasis (Bai et al, 2017), control brown adipocyte differentiation (Zhao et al, 2014), and maintain its morphology (Alvarez-Dominguez et al, 2015). Several lncRNAs recognized from human adipose tissue were characterized to be related to adipogenesis (Ding et al, 2018). Zhou et al observed down regulation of MEG3 during adipogenesis and confirmed its role in human adipogenic differentiation via knockdown assay (Li et al, 2017)

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