MicroRNA-125a-5p Mediates 3T3-L1 Preadipocyte Proliferation and Differentiation.

Yan Xu,Yanzhi Jiang,Shunhua Zhang,Jingjing Du,Dongmei Jiang,Xuewei Li,Peiwen Zhang,Li Zhu,Qiang Li,Xue Zhao,Guoqing Tang,Anan Jiang,Jinyong Wang

doi:10.3390/molecules23020317

Abstract

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional levels. In this study, we showed that miR-125a-5p was expressed at lower levels in the adipose tissues of high-fat diet (HFD)-fed mice than the normal chow (NCW)-fed mice. MiR-125a-5p expression were strongly up-regulated by nearly five-fold, when 3T3-L1 preadipocyte were induced and differentiated into mature adipocytes. Functional analysis indicated that overexpression of miR-125a-5p promoted 3T3-L1 preadipocyte proliferation and inhibited its differentiation. By contrast, inhibition of miR-125a-5p repressed 3T3-L1 preadipocyte proliferation and accelerated its differentiation. Furthermore, a dual-luciferase reporter assay demonstrated that signal transducer and activator of transcription 3 (STAT3) is a direct target gene of miR-125a-5p during 3T3-L1 preadipocyte differentiation. Further analysis confirmed that the process of miR-125a-5p inhibiting 3T3-L1 preadipocyte differentiation might be associated with the regulation of fatty acid metabolism related genes. Taken together, our results indicated that miR-125a-5p might promote 3T3-L1 preadipocyte proliferation, whereas inhibiting 3T3-L1 preadipocyte differentiation by negatively regulating STAT3.

Highlights

In the past few decades, obesity or overweight were usually considered a major nutritional health problem in developed countries [1]
By transfecting miR-125a-5p mimics, inhibitors or the negative control into 3T3-L1 preadipocyte, we showed that miR-125a-5p promoted 3T3-L1 preadipocyte proliferation via affecting cell cycle-regulated factors, whereas inhibited differentiation through directly targeting signal transducer and activator of transcription 3 (STAT3), and this effect might be associated with fatty acids oxidation and synthesis
Our study has shown that ssc-miR-125a-5p was expressed at lower levels in adipose tissues containing large volumes of adipocytes, of which increasing retroperitoneal adipose (RAD), greater omentum (GOM) and mesenteric adipose (MAD) have been demonstrated to be associated with several diseases [20] (Figure 1B), and Ji et al [21] demonstrated that ssc-miR-125a-5p inhibited porcine preadipocyte differentiation by targeting ERRα

Summary

Introduction

In the past few decades, obesity or overweight were usually considered a major nutritional health problem in developed countries [1]. The prevalence of obesity is significantly increasing on a world scale, which has reached epidemic proportions and become among the most common human health problems in developed and developing countries [2,3]. Nearly half a billion of the world’s population are considered to be overweight or obese [4]. The proportion of adults with a body-mass index (BMI) of 25 kg/m2 was greatly increased between 1980 and 2013 from 28.8% to 36.9% in men, and from 29.8% to 38.0% in women [5]. Limiting overweight and treating obesity are important for treating obesity-related diseases and improving human health

Methods

Results

Conclusion