MiRNA-181a Regulates Adipogenesis by Targeting Tumor Necrosis Factor-α (TNF-α) in the Porcine Model

PLoS One

Qianyun Xi¹  Xiao Chen²  Qien Qi³  Gang Shu³  Hongyi Li³  Lizeng Guan³  Qingyan Jiang³  Yongliang Zhang³  Li Yuan³ 

[1] College of Life Science, Xiamen University, Xiamen, China;Fujian Provincial Key Laboratory of Preventive Veterinary Medicine and Biotechnology, College of Life Science, Longyan University, Fujian, China;Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, China

关键词: Adipocytes;    Transfection;    Adipocyte differentiation;    Gene expression;    MicroRNAs;    Lipogenesis;    Small interfering RNAs;    3' UTR;   

DOI  :  10.1371/journal.pone.0071568

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Adipogenesis is tightly regulated by altering gene expression, and TNF-α is a multifunctional cytokine that plays an important role in regulating lipogenesis. MicroRNAs are strong post-transcriptional regulators of cell differentiation. In our previous work, we found high expression of miR-181a in a fat-rich pig breed. Using bioinformatic analysis, miR-181a was identified as a potential regulator of TNF-α. Here, we validated TNF-α as the target of miR-181a by a dual luciferase assay. In response to adipogenesis, a mimic or inhibitor was used to overexpress or reduce miR-181a expression in porcine pre-adipocytes, which were then induced into mature adipocytes. Overexpression of miR-181a accelerated accumulation of lipid droplets, increased the amount of triglycerides, and repressed TNF-α protein expression, while the inhibitor had the opposite effect. At the same time, TNF-alpha rescued the increased lipogenesis by miR181a mimics. Additionally, miR-181a suppression decreased the expression of fatty synthesis associated genes PDE3B (phosphodiesterase 3B), LPL (lipoprotein lipase), PPARγ (proliferator-activated receptor-γ), GLUT1(glucose transporter), GLUT4, adiponectin and FASN (fatty acid synthase), as well as key lipolytic genes HSL (hormone-sensitive lipase) and ATGL (adipose triglyceride lipase) as revealed by quantitative real-time PCR. Our study provides the first evidence of the role of miR-181a in adipocyte differentiation by regulation of TNF-α, which may became a new therapeutic target for anti-obesity drugs.

【 授权许可】

CC BY