MicroRNA-126b-5p Exacerbates Development of Adipose Tissue and Diet-Induced Obesity.

Linyuan Shen,Jin He,Guoqing Tang,Li Zhu,Lili Niu,Xiaoxia Hao,Xuewei Li,Ye Zhao,Lei Chen,Yanzhi Jiang,Shunhua Zhang,Lin Bai

doi:10.3390/ijms221910261

Abstract

Obesity has become a worldwide epidemic, caused by many factors such as genetic regulatory elements, unhealthy diet, and lack of exercise. MicroRNAs (miRNAs) are non-coding single-stranded RNA classes, which are about 22 nucleotides in length and highly conserved among species. In the last decade, a series of miRNAs were identified as therapeutic targets for obesity. In the present study, we found that miR-126b-5p was associated with adipogenesis. miR-126b-5p overexpression promoted the proliferation of 3T3-L1 preadipocytes by upregulating the expression of proliferation-related genes and downregulating the expression of apoptosis-related genes; the inhibition of miR-126b-5p gave rise to opposite results. Similarly, miR-126b-5p overexpression could promote the differentiation of 3T3-L1 preadipocytes by increasing the expression of lipid deposition genes and triglyceride (TG) and total cholesterol (TC) levels. Moreover, luciferase reporter assay demonstrated that adiponectin receptor 2 (Adipor2) and acyl-CoA dehydrogenase, long chain (ACADL) were the direct target genes of miR-126b-5p. Moreover, overexpression of miR-126b-5p could exacerbate the clinical symptoms of obesity when mice were induced by a high-fat diet, including increased adipose tissue weight, adipocyte volume, and insulin resistance. Interestingly, overexpression of miR-126b-5p in preadipocytes and mice could significantly increase total fatty acid content and change the fatty acid composition of adipose tissue. Taken together, the present study showed that miR-126b-5p promotes lipid deposition in vivo and in vitro, indicating that miR-126b-5p is a potential target for treating obesity.

Highlights

As the quality of life continues to improve, overweight and obesity are becoming a noticeable trend in most countries
The results showed that the total fatty acid content was significantly upregulated, which might have been caused by the remarkable upregulation of the saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) content
ACOX2 significantly decreased when the H-126 group was compared to the H-NC group (Figure 5Q). These findings demonstrated that overexpression of miR-126b-5p in the mice fed with a high-fat diet exacerbated obesity

Summary

Introduction

As the quality of life continues to improve, overweight and obesity are becoming a noticeable trend in most countries. A survey in 2017 showed that the prevalence of overweight was 33.8% (body mass index, BMI ≥ 24.0 kg/m2 , according to Chinese criteria), and the obesity prevalence was 6.3% (BMI ≥ 28.0 kg/m2 ) among 15.8 million men in Chinese rural areas [5]. Other studies showed that global obesity prevalence would reach 18% in men and surpass 21% in women by 2025 if obesity is not controlled [6]. Obesity or overweight has become a global public health problem that cannot be ignored and should be dealt with urgently. MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA, about 22 nucleotides in length and highly conserved among species. MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA, about 22 nucleotides in length and highly conserved among species. miRNAs bind to the 30 untranslated region (30 UTR) of target genes, disrupting their mRNA inactivation or transcription

Methods

Findings

Discussion

Conclusion