Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with aging

Iordanes Karagiannides, Thomas Thomou, Tamara Tchkonia, Tamar Pirtskhalava, Kyriakos E. Kypreos, Andrew Cartwright, Georgia Dalagiorgou, Timothy L. Lash, R. Stephen, Nikolai A. Timchenko, James L. Kirkland

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45 Scopus citations

Abstract

Preadipocyte differentiation capacity declines between middle and old age. Expression of the adipogenic transcription factors, CCAAT/enhancer-binding protein (C/EBP) α and peroxisome proliferator-activated receptor γ (PPARγ), is lower in differentiating preadipocytes from old than young animals, although no age-related changes occur in C/EBPβ mRNA, which is upstream of C/EBPα and PPARγ. C/EBPβ-liver-enriched inhibitory protein (C/EBPβ-LIP), a truncated C/EBPβ isoform that is a dominant inhibitor of differentiation, increases with aging in rat fat tissue and preadipocytes. CUG triplet repeat-binding protein-1 (CUGBP1) binds to C/EBPβ mRNA, increasing C/EBPβ-LIP translation. Abundance and nucleotide binding activity of CUGBP1 increased with aging in preadipocytes. CUGBP1 overexpression in preadipocytes from young animals increased C/EBPβ-LIP and impaired adipogenesis. Decreasing CUGBP1 in preadipocytes from old rats by RNA interference reduced C/EBPβ-LIP abundance and promoted adipogenesis. Tumor necrosis factor-α, levels of which are elevated in fat tissue with aging, increased CUGBP1 protein, CUGBP1 binding activity, and C/EBPβ-LIP in preadipocytes from young rats. Thus, CUGBP1 contributes to regulation of adipogenesis in primary preadipocytes and is responsive to tumor necrosis factor-α. With aging, preadipocyte CUGBP1 abundance and activity increases, resulting in enhanced translation of the C/EBPβ-LIP isoform, thereby blocking effects of adipogenic transcription factors, predisposing preadipocytes from old animals to resist adipogenesis. Altered translational processing, possibly related to changes in cytokine milieu and activation of stress responses, may contribute to changes in progenitor differentiation and tissue function with aging.

Original languageEnglish (US)
Pages (from-to)23025-23033
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number32
DOIs
StatePublished - Aug 11 2006

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Karagiannides, I., Thomou, T., Tchkonia, T., Pirtskhalava, T., Kypreos, K. E., Cartwright, A., Dalagiorgou, G., Lash, T. L., Stephen, R., Timchenko, N. A., & Kirkland, J. L. (2006). Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with aging. Journal of Biological Chemistry, 281(32), 23025-23033. https://doi.org/10.1074/jbc.M513187200