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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

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Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene

T Tanaka1, N Yoshida, T Kishimoto

  • 1Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663, Japan.

The EMBO Journal
|February 21, 1998
PubMed

Insights

CCAAT-enhancer-binding protein beta (C/EBPbeta) and C/EBPdelta are crucial for adipocyte differentiation. Mice lacking both C/EBPbeta and C/EBPdelta show severe defects in fat development and survival.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Adipocyte differentiation is a complex process regulated by transcription factors.
  • CCAAT-enhancer-binding protein (C/EBP) family members are known to play roles in adipogenesis.
  • The specific in vivo roles of C/EBPbeta and C/EBPdelta in terminal adipocyte differentiation require further elucidation.

Purpose of the Study:

  • To investigate the in vivo function of C/EBPbeta and C/EBPdelta in adipocyte differentiation.
  • To determine the necessity of C/EBPbeta and C/EBPdelta for the expression of other key adipogenic factors like C/EBPalpha and PPARgamma.

Main Methods:

  • Generation of knockout mice lacking C/EBPbeta and/or C/EBPdelta using gene targeting.
  • Analysis of neonatal and adult mice for survival rates, adipose tissue morphology, and fat pad weight.
  • Assessment of gene expression for C/EBPalpha and PPARgamma in adipose tissues of knockout mice.

Main Results:

  • Mice lacking both C/EBPbeta and C/EBPdelta (C/EBPbeta(-/-).delta(-/-)) exhibited an 85% neonatal mortality rate.
  • C/EBPbeta(-/-).delta(-/-) mice showed a significant reduction in interscapular brown adipose tissue lipid droplet accumulation and epididymal fat pad weight.
  • Adipose tissues in C/EBPbeta(-/-).delta(-/-) mice displayed normal C/EBPalpha and PPARgamma expression but impaired adipogenesis.

Conclusions:

  • C/EBPbeta and C/EBPdelta act synergistically to promote terminal adipocyte differentiation in vivo.
  • While C/EBPbeta and C/EBPdelta are not strictly required for C/EBPalpha and PPARgamma induction, their absence prevents complete adipocyte differentiation.
  • These findings highlight the essential and non-redundant roles of C/EBPbeta and C/EBPdelta in adipose tissue development.

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