Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity.

Zhenjun Wang,Ke Cao,Ganbin Li,Jiagang Han,Zhiwei Zhai,Haoyu Zhang,Lei Yang

doi:10.1007/s11010-022-04362-y

Zhenjun Wang, Ke Cao

Open Access

https://doi.org/10.1007/s11010-022-04362-y

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Abstract

Obesity is becoming an epidemic of widespread concern, but the underlying causes remain elusive. In this study, whole transcriptome RNA sequencing revealed differential profiles of noncoding (nc) RNAs and mRNAs in visceral adipose tissue from obese (BMI > 32.5kg/m2) and lean (BMI < 20kg/m2) individuals, with 1920 differentially expressed genes, 1466 long noncoding (lnc) RNAs, 122 micro (mi) RNAs, and 52 circular (circ) RNAs identified. Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these ncRNAs were involved in inflammation-related pathways that included cytokine-cytokine receptor interaction, the tumor necrosis factor and nuclear factor kappa B signaling pathways. The results indicated a critical role of inflammation in the pathogenesis of obesity. The network interaction of lncRNA, circRNA, and miRNA revealed a competing endogenous (ce) RNA network that was associated with inflammation. The ceRNA network included circORC5/miR-197-5p/TNFRSF10D and circNTRK2/miR-760/LAT, which were dysregulated in obese patients. In conclusion, this whole transcriptome study provided a pool of data that will be useful for identifying biomarkers of obesity and identified an obesity-associated ceRNA network that is regulated by circORC5 and circNTRK2.

Highlights

Obesity is increasing worldwide and is associated with metabolic diseases, such as diabetes, hypertension, cardiovascular disease, as well as an increased risk of malignancy[1, 2]
Patients with a body mass index (BMI) ≥ 32.5 kg/m2 were included in an obese group and those with a BMI ≤ 20 kg/m2 were included in a normal-weight group
Accumulating evidence confirms that excessive energy storage in visceral adipose tissue (VAT) leads to dysregulated secretion of adipokines and cytokines and state of chronic, low-grade inflammation and insulin resistance associated with obesity [18, 19]

Summary

Introduction

Obesity is increasing worldwide and is associated with metabolic diseases, such as diabetes, hypertension, cardiovascular disease, as well as an increased risk of malignancy[1, 2]. Obesity is characterized by an imbalance between caloric intake and energy expenditure resulting in excessive accumulation of fat in visceral adipose tissue (VAT)[3]. In addition to energy storage, VAT is an endocrine organ, secreting adipose-derived cytokines, leptin, visfatin, and adiponectin [4]. Obesity is accompanied by hyperplasia and enlargement of adipocytes and increased secretion of multiple adipokines and proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis (TNF)-α that lead to chronic, low-grade local inflammation and insulin resistance [5, 6]. MiRNAs are small endogenous ncRNAs with 20–22 bps. Several recent studies reported that dysregulated miRNAs enhanced chronic inflammation, insulin resistance, adipogenesis, and angiogenesis in VAT and promoted the process of obesity [8, 9]. CircRNAs are ncRNAs with a closed loop structure and reverse splicing of its 5′

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