title: Altered expression of C/EBP family members results in decreased adipogenesis with aging.
abstract: 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/EBP alpha 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 alpha-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP beta, which modulates C/EBP alpha-expression, did not change with 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 impaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta 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.
authors.affiliation: Department of Medicine, Boston University, Boston, Massachusetts 02118, USA.
authors.forename: I
authors.initials: I
authors.lastname: Karagiannides
authors.forename: T
authors.initials: T
authors.lastname: Tchkonia
authors.forename: D E
authors.initials: DE
authors.lastname: Dobson
authors.forename: C M
authors.initials: CM
authors.lastname: Steppan
authors.forename: P
authors.initials: P
authors.lastname: Cummins
authors.forename: G
authors.initials: G
authors.lastname: Chan
authors.forename: K
authors.initials: K
authors.lastname: Salvatori
authors.forename: M
authors.initials: M
authors.lastname: Hadzopoulou-Cladaras
authors.forename: J L
authors.initials: JL
authors.lastname: Kirkland
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000254:growth & development*; D000375:Aging / Q000502:physiology*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002478:Cells, Cultured; D005810:Multigene Family / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C545014:Cebpb protein, rat; D014157:Transcription Factors