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Related Experiment Videos

E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2.

Yang Yang1, Hongkui Wei1, Tongxing Song1

  • 1Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.

Molecular and Cellular Endocrinology
|April 19, 2017
PubMed
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E4 promoter-binding protein 4 (E4BP4) promotes fat cell differentiation by regulating glucocorticoid receptor (GR) activity. E4BP4 represses COX2, enhancing glucocorticoid-induced adipogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Endocrinology

Background:

  • Adipogenesis, the process of fat cell formation, is regulated by glucocorticoids through transcriptional control of glucocorticoid receptor (GR) target genes.
  • The precise mechanisms of GR involvement in adipogenesis remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of E4 promoter-binding protein 4 (E4BP4) in adipogenic differentiation.
  • To investigate the regulatory pathway involving E4BP4, glucocorticoids, and COX2 during adipogenesis.

Main Methods:

  • Gain-of-function and loss-of-function studies in 3T3-L1 preadipocytes.
  • Analysis of E4BP4 induction by dexamethasone via GR and cAMP response element-binding protein (CREB).
  • Promoter deletion analysis to assess E4BP4's effect on COX2 promoter activity.
Keywords:
3T3-L1AdipogenesisCOX2DexamethasoneE4BP4GR

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Main Results:

  • E4BP4 functions as a positive regulator of adipogenesis in 3T3-L1 cells.
  • Dexamethasone significantly induces E4BP4 expression through GR and CREB.
  • E4BP4 knockdown abrogates dexamethasone-induced adipogenesis; E4BP4 overexpression partially mimics dexamethasone's effects.
  • E4BP4 transcriptionally represses the COX2 promoter, and COX2 overexpression counteracts E4BP4's pro-adipogenic effects.

Conclusions:

  • E4 promoter-binding protein 4 (E4BP4) is a crucial pro-adipogenic transcription factor.
  • E4BP4 mediates glucocorticoid-stimulated adipocyte differentiation by trans-repressing COX2.