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B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation

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Abstract

Btg2, a member of a family of antiproliferative proteins, is involved in downregulation of the JAK2–Stat3 signaling pathway. Here, we present evidence that the inhibitory effect of Btg2 on adipogenesis is suppressed by the proadipogenic activity of the Stat3 signaling pathway. Btg2 expression fluctuates during adipogenic differentiation of preadipocytes. Btg2 is also expressed at different levels in fat tissues from lean and obese mice. Furthermore, knockdown of Btg2 expression enhanced lipid accumulation and upregulated the expression of adipogenic marker genes. To gain insights into the molecular mechanisms of Btg2 action in adipocytes, adipocytes were treated with previously identified bioactive compounds and the expression of Btg2 was assessed. This effort identified the small molecule WP1066, a known Stat3 inhibitor, as an inducer of Btg2 expression. In line with this observation, siRNA-mediated silencing of Stat3 resulted in upregulated Btg2 expression and decreased lipid accumulation. Furthermore, siRNA-mediated silencing of Btg2 attenuated WP1066-mediated inhibition of adipocyte differentiation. We discuss a model for the role of Btg2 in adipogenesis and propose that Btg2 and Stat3 act in a functional hierarchy.

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Abbreviations

Btg2:

B cell translocation gene 2

Stat3:

Signal transducer and activator of transcription 3

ND:

Normal chow diet

HFD:

High-fat diet

siRNA:

Small interfering RNA

DMSO:

Dimethylsulfoxide

Pparγ:

Peroxisome proliferator-activated receptor γ

C/ebpα:

CCAAT-enhancer-binding proteins α

aP2:

Adipocyte protein 2

adipoQ:

Adiponectin

CD36:

Cluster of differentiation 36

C/ebpδ:

CCAAT/enhancer binding protein delta

Bcl2:

B-cell CLL/lymphoma 2

Klf5:

Krüppel-like factor 5

36b4:

Acidic ribosomal phosphoprotein P0

DMI:

Dexamethasone, IBMX, and insulin

PCR:

Polymerase chain reaction

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Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2010-0002792 and NRF-2012R1A1A2038502 to J.W.H., NRF-2011-0014302 and NRF-2013R1A1A2060447 to K.W.P.).

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Authors and Affiliations

  1. Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea

    Suji Kim & Kye Won Park

  2. Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 17104, Korea

    Joung-Woo Hong

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  1. Suji Kim
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Correspondence to Joung-Woo Hong or Kye Won Park.

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Kim, S., Hong, JW. & Park, K.W. B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation. Mol Cell Biochem 413, 145–153 (2016). https://doi.org/10.1007/s11010-015-2648-z

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  • DOI: https://doi.org/10.1007/s11010-015-2648-z

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