Altered expression of C/EBP family members results in decreased adipogenesis with aging

Iordanes Karagiannides, Tamara Tchkonia, Deborah E. Dobson, Claire M. Steppan, Patrice Cummins, Gabriel Chan, Keith Salvatori, Margarita Hadzopoulou-Cladaras, James L. Kirkland

Research output: Contribution to journalArticlepeer-review

125 Scopus citations


Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-α, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBPα in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBPα-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBPβ, which modulates C/EBPα-expression, did not change with age, but the truncated, dominant-negative C/EBPβ-liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBPβ-LIP in preadipocytes from young rats impaired adipogenesis. C/EBPδ, which acts with full-length C/EBPβ to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.

Original languageEnglish (US)
Pages (from-to)R1772-R1780
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6 49-6
StatePublished - 2001


  • C/EBPα
  • C/EBPβ
  • C/EBPδ
  • Differentiation
  • Preadipocytes

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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