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

Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte dif ferentiation decrease between middle and old age. We show that expression o f CCAAT/enhancer binding protein (C/EBP)-alpha, a key regulator of adipogen esis and fat cell function, declined substantially with aging in differenti ating preadipocytes cultured under identical conditions from rats of variou s ages. Overexpression of C/EBP alpha in preadipocytes cultured from old ra ts restored capacity to differentiate into fat cells, indicating that downs tream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBP alpha -expression also decreased with age in fat ti ssue from three different depots and in isolated fat cells. The overall lev el of C/EBP beta, which modulates C/EBP alpha -expression, did not change w ith age, but the truncated, dominant-negative C/EBP beta -liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP beta -LIP in preadipocytes from young rats i mpaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta t o enhance adipogenesis, decreased with age. Thus processes intrinsic to adi pose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.