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miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and Sertad2

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Abstract

Differentiation of adipocytes and their aggregation to adipose tissue are critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play important roles in adipogenesis and lipid metabolism. miR-128-3p may contribute to adipose tissue development according to the previous studies. However, the role of miR-128-3p in the process of preadipocyte differentiation and lipid metabolism is not yet understood. The purpose of this research was to investigate the biological function and molecular mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR-128-3p was downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-128-3p obstructed the expressions of adipogenic marker genes as well as the lipid droplets accumulation and triglyceride content, suggesting the importance of miR-128-3p for adipogenesis. Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3-L1 preadipocytes. Further evidences showed that, as a negative regulator of adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated receptor γ (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte differentiation, and miR-128-3p could also bind with SERTA domain containing 2 (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition, inhibition of Sertad2 with siRNA displayed the same effects as overexpression of miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte differentiation and promotion of lipolysis. Taken together, this study offers profound insight into the mechanism of miRNA-mediated adipogenesis and lipid metabolism.

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Abbreviations

Cebpa :

CCAAT/enhancer binding protein α

Pparg :

Peroxisome proliferator-activated receptor γ

Fas :

Fatty acid synthase

Ap2 :

Adipocyte fatty acid binding protein

Atgl :

Triglyceride lipase

Hsl :

Hormone-sensitivelipase

Sertad2 :

SERTA domain containing 2

FFA:

Free fatty acid

QPCR:

Quantitative real-time polymerase chain reaction

UTR:

Untranslated region

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Funding

This research was funded by the National Natural Science Foundation of China (31401097), Key Research and Development Program of Hunan Province of China (2016NK2169, 2017NK2331), Open Research Program of Hunan Provincial Key Laboratory (2017TP1030), and National High Technology Research and Development Program of China (2013AA102503).

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  1. Chen Chen and Yinglin Peng contributed equally to this work

Authors and Affiliations

  1. Hunan Institute of Animal & Veterinary Science, Changsha, 410131, People’s Republic of China

    Chen Chen, Yuan Deng, Xionggui Hu, Huibo Ren, Ji Zhu, Shengcai Fu, Julan Xie & Yinglin Peng

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  1. Chen Chen
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  2. Yuan Deng
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  3. Xionggui Hu
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Correspondence to Chen Chen or Yinglin Peng.

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Chen, C., Deng, Y., Hu, X. et al. miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and Sertad2. J Physiol Biochem 74, 381–393 (2018). https://doi.org/10.1007/s13105-018-0625-1

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