Role of C/EBP¦Â-LAP and C/EBP¦Â-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes

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• 作者：Stefan Lechner^a ; ^{stefanlechner1@gmx.at} ; Maria C. Mitterberger^a ; ^{Maria.Mitterberger@uibk.ac.at} ; Monika Mattesich^b ; ^{Monika.Mattesich@i-med.ac.at} ; Werner Zwerschke^a ; ^{Werner.Zwerschke@uibk.ac.at}
• 关键词：Human adipose-derived stromal/progenitor cells ; Adipocytes ; Adipogenesis ; C/EBP¦Â ; LAP ; LIP ; Ubiquitin/proteasome system
• 刊名：Differentiation
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：85
• 期：1-2
• 页码：20-31
• 全文大小：1157 K

文摘

We investigated the role of the major isoforms of CCAAT enhancer binding protein ¦Â (C/EBP¦Â), C/EBP¦Â-LAP and C/EBP¦Â-LIP, in adipogenesis of human white adipose-derived stromal/progenitor cells (ASC). C/EBP¦Â gene expression was transiently induced early in adipogenesis. At later stages, in immature adipocytes, the C/EBP¦Â mRNA and protein levels declined. The C/EBP¦Â-LIP protein steady-state level decreased considerably stronger than the C/EBP¦Â-LAP level and the C/EBP¦Â-LIP half-life was significantly shorter than the C/EBP¦Â-LAP half-life. The turn-over of both C/EBP¦Â-isoforms was regulated by ubiquitin/proteasome-dependent degradation. These data suggest that the protein stability of the C/EBP¦Â-isoforms is differentially regulated in the course of adipogenesis and in immature adipocytes. Constitutive overexpression of C/EBP¦Â-LIP had antiadipogenic activity in human ASC. C/EBP¦Â-LAP, which promotes adipogenesis in mouse 3T3-L1 preadipocytes by directly activating expression of the adipogenic keyregulator PPAR¦Ã2, induced the expression of PPAR¦Ã2 and of the adipocyte differentiation gene product FABP4 in confluent ASC in the absence of adipogenic hormones. At later stages after hormone cocktail-induced adipogenesis, in immature adipocytes, constitutive overexpression of C/EBP¦Â-LAP led to reduced expression of PPAR¦Ã2 and FABP4, C/EBP¦Á expression was downregulated and the expression of the adipocyte differentiation gene products adiponectin and leptin was impaired. These findings suggest that constitutive overexpression of C/EBP¦Â-LAP induces adipogenesis in human ASC and negatively regulates the expression of adipogenic regulators and certain adipocyte differentiation gene products in immature adipocytes. We conclude the regulation of both C/EBP¦Â gene expression and C/EBP¦Â-LIP and C/EBP¦Â-LAP protein turn-over plays an important role for the expression of adipogenic regulators and/or adipocyte differentiation genes in early adipogenic differentiation of human ASC and at later stages in human immature adipocytes.