Elsevier

Gene

Volume 575, Issue 2, Part 3, 10 January 2016, Pages 761-764
Gene

Short communication
MicroRNA-23a regulates 3T3-L1 adipocyte differentiation

https://doi.org/10.1016/j.gene.2015.09.060Get rights and content

Highlights

  • The role of miRNA-23a in adipocyte differentiation were firstly investigated.

  • miRNA-23a influences lipid accumulation and triglyceride content was observed.

  • miRNA-23a changes lipogenic transcription, fatty acid synthesis and fatty acid transport.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs, which are involved in regulation of a variety of biological processes. Since previous studies regarding the role of miRNAs in the regulation of adipogenic differentiation have shown that miRNA-27a, one member of miRNA-23a∼27a∼24 cluster, could suppress adipogenesis. We now investigated whether miRNA-23a regulates adipogenic differentiation. In the present study, we showed that the expression of miRNA-23a is decreased during the process of adipogenic differentiation. Over-expression of miRNA-23a decreased lipid accumulation and triglyceride content in 3T3-L1 adipocytes. Our results also demonstrated that miRNA-23a decreases mRNA levels of adipocyte-specific genes involved in lipogenic transcription, fatty acid synthesis and fatty acid transport. These findings suggested miRNA-23a to be a new type of adipogenic depressor and to play an important role in regulating adipocyte differentiation.

Introduction

MicroRNAs (miRNAs) are endogenous small, non-coding RNAs of about 22 nucleotide in length, and able to post-transcriptionally regulate gene expression by complementarily binding to the 3′-untranslated region (3′-UTR) of their target genes (Ambros, 2004). Among the large number of biological processes regulated by miRNAs, fat development and lipogenesis are particularly important because they are closely related to adipose tissue function. Adipose tissue is not only an energy storage organ, but also fulfills important immune functions (Tilg and Moschen, 2006). Regulatory mechanisms regarding adipose tissue gain more and more interest due to the increasing prevalence of obesity, diabetes and cardiovascular diseases in human being (Hajer et al., 2008). Exploring the role of miRNAs in the regulation of lipid metabolism may contribute to our understanding of these diseases.

The role of miRNAs in fat metabolism was first described in Drosophila melanogaster, where the loss of miRNA-14 resulted in an increased content of triacylglycerol and diacylglycerol (Xu et al., 2003). Furthermore, miRNA-375 was found to promote 3T3-L1 adipocyte differentiation (Ling et al., 2011). miRNA-143 may target mitogen-activated protein kinase, and thus stimulate adipocyte differentiation (Esau et al., 2004). Interestingly, miRNA-27a, miRNA-23a and miRNA-24–2 were determined to be a cluster, because they exhibited similar expression patterns and cooperative physiological effects in different disease condition (Chhabra et al., 2009, Chhabra et al., 2010, Hassan et al., 2010). A recent study demonstrated that miRNA-27a inhibited adipogenic differentiation by blockading the expression of PPARγ and C/EBPα gene (Lin et al., 2009). However, the underlying roles of miRNA-23a in adipogenic differentiation have not been clarified. The mouse 3T3-L1 pre-adipocyte cell line is widely used as an adipocyte differentiation model. In order to evaluate the effect of miRNA-23a regulating adipocyte differentiation, we treated 3T3-L1 cells with synthesized miRNA-23a mimic or inhibitor to augment or decrease its expression level, respectively in this study.

Section snippets

Cell culture

3T3-L1 pre-adipocytes were maintained in Dulbecco's modified Eagle's medium (DMEM, Hyclone) containing 10% fetal bovine serum (FBS, Hyclone) at 5% CO2 and 37 °C. To induce differentiation, post-confluent 3T3-L1 pre-adipocytes were incubated for 2 days in a differentiation media (DM) containing 10% FBS, 0.5 mM 3-isobutyl-1-methylxanthine, 1 μM dexamethasone, and 5 μg of insulin/ml. The medium was replaced every second day with DMEM containing 10% FBS and 5 μM of insulin/ml, and the process was kept on

Expression of miRNA-23a in 3T3-L1 adipocytes

miRNA-23a is a member of miRNA-23a  27a  24 cluster (Fig. 1A), which has a significantly negative correlation with adipocyte volume in vivo according to our previous studies (r =  0.78, P < 0.01, Fig. 2B) (Li et al., 2012). To explore the potential role of miRNA-23a in adipogenic differentiation, we measured the expression levels of miRNA-23a in 3T3-L1 cells during differentiation into mature adipocytes. As shown in Fig. 1C, the expression of miRNA-23a was decreased more than 4-fold in 3T3-L1

Conclusion

Our results confirmed the important role of miRNA-23a in 3T3-L1 pre-adipocyte differentiation. During the process of adipocyte differentiation, expression levels of miRNA-23a were found to be decreased. Upon over-expression of this miRNA, lipid accumulation and triglyceride content in 3T3-L1 cells were depressed. In addition, miRNA-23a was shown to suppress the expression of different adipocyte marker genes related to adipocyte differentiation. We therefore can draw a conclusion that miRNA-23a

Acknowledgments

The study was supported by the Sichuan Sci & Tech Support Program (No. 2013NZ0041, and 2013NZ0056), the earmarked fund for China Agriculture Research System (No. CARS-36-05B), the Chinese National Sci & Tech Support Program (No. 2013BAD20B07), and the International Science & Technology Cooperation Program of China (2014DFA31260).

References (12)

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These authors contributed equally to this work.

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