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Am J Physiol Regul Integr Comp Physiol 280: R1772-R1780, 2001;
0363-6119/01 $5.00
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Vol. 280, Issue 6, R1772-R1780, June 2001

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

Iordanes Karagiannides1,2,*, Tamara Tchkonia1,*, Deborah E. Dobson3, Claire M. Steppan3, Patrice Cummins1, Gabriel Chan1, Keith Salvatori1, Margarita Hadzopoulou-Cladaras1, and James L. Kirkland1,3

1 Departments of Medicine, 2 Pathology, and 3 Biochemistry, Boston University, Boston, Massachusetts 02118

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)-alpha , 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/EBPalpha 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/EBPalpha -expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBPbeta , which modulates C/EBPalpha -expression, did not change with age, but the truncated, dominant-negative C/EBPbeta -liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBPbeta -LIP in preadipocytes from young rats impaired adipogenesis. C/EBPdelta , which acts with full-length C/EBPbeta 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.

preadipocytes; differentiation; C/EBPalpha ; C/EBPbeta ; c/EBPdelta

* I. Karagiannides and T. Tchkonia contributed equally to this work.




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