I. Karagiannides et al., Altered expression of C/EBP family members results in decreased adipogenesis with aging, AM J P-REG, 280(6), 2001, pp. R1772-R1780
Citations number
62
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
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.