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

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)- , 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/EBP 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/EBP -expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP , which modulates C/EBP -expression, did not change with age, but the truncated, dominant-negative C/EBP -liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP -LIP in preadipocytes from young rats impaired adipogenesis. C/EBP , which acts with full-length C/EBP 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/EBP ; C/EBP ; c/EBP * I. Karagiannides and T. Tchkonia contributed equally to this work.