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Role of C/EBPβ-LAP and C/EBPβ-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes.
Differentiation. 2013 Jan; 85(1-2):20-31.D

Abstract

We investigated the role of the major isoforms of CCAAT enhancer binding protein β (C/EBPβ), C/EBPβ-LAP and C/EBPβ-LIP, in adipogenesis of human white adipose-derived stromal/progenitor cells (ASC). C/EBPβ gene expression was transiently induced early in adipogenesis. At later stages, in immature adipocytes, the C/EBPβ mRNA and protein levels declined. The C/EBPβ-LIP protein steady-state level decreased considerably stronger than the C/EBPβ-LAP level and the C/EBPβ-LIP half-life was significantly shorter than the C/EBPβ-LAP half-life. The turn-over of both C/EBPβ-isoforms was regulated by ubiquitin/proteasome-dependent degradation. These data suggest that the protein stability of the C/EBPβ-isoforms is differentially regulated in the course of adipogenesis and in immature adipocytes. Constitutive overexpression of C/EBPβ-LIP had antiadipogenic activity in human ASC. C/EBPβ-LAP, which promotes adipogenesis in mouse 3T3-L1 preadipocytes by directly activating expression of the adipogenic keyregulator PPARγ2, induced the expression of PPARγ2 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/EBPβ-LAP led to reduced expression of PPARγ2 and FABP4, C/EBPα 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/EBPβ-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/EBPβ gene expression and C/EBPβ-LIP and C/EBPβ-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.

Authors+Show Affiliations

Department of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research of the University of Innsbruck, Rennweg 10, Innsbruck, Austria. stefanlechner1@gmx.atNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23314288

Citation

Lechner, Stefan, et al. "Role of C/EBPβ-LAP and C/EBPβ-LIP in Early Adipogenic Differentiation of Human White Adipose-derived Progenitors and at Later Stages in Immature Adipocytes." Differentiation; Research in Biological Diversity, vol. 85, no. 1-2, 2013, pp. 20-31.
Lechner S, Mitterberger MC, Mattesich M, et al. Role of C/EBPβ-LAP and C/EBPβ-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes. Differentiation. 2013;85(1-2):20-31.
Lechner, S., Mitterberger, M. C., Mattesich, M., & Zwerschke, W. (2013). Role of C/EBPβ-LAP and C/EBPβ-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes. Differentiation; Research in Biological Diversity, 85(1-2), 20-31. https://doi.org/10.1016/j.diff.2012.11.001
Lechner S, et al. Role of C/EBPβ-LAP and C/EBPβ-LIP in Early Adipogenic Differentiation of Human White Adipose-derived Progenitors and at Later Stages in Immature Adipocytes. Differentiation. 2013;85(1-2):20-31. PubMed PMID: 23314288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of C/EBPβ-LAP and C/EBPβ-LIP in early adipogenic differentiation of human white adipose-derived progenitors and at later stages in immature adipocytes. AU - Lechner,Stefan, AU - Mitterberger,Maria C, AU - Mattesich,Monika, AU - Zwerschke,Werner, Y1 - 2013/01/11/ PY - 2012/05/24/received PY - 2012/09/20/revised PY - 2012/11/26/accepted PY - 2013/1/15/entrez PY - 2013/1/15/pubmed PY - 2013/11/5/medline SP - 20 EP - 31 JF - Differentiation; research in biological diversity JO - Differentiation VL - 85 IS - 1-2 N2 - We investigated the role of the major isoforms of CCAAT enhancer binding protein β (C/EBPβ), C/EBPβ-LAP and C/EBPβ-LIP, in adipogenesis of human white adipose-derived stromal/progenitor cells (ASC). C/EBPβ gene expression was transiently induced early in adipogenesis. At later stages, in immature adipocytes, the C/EBPβ mRNA and protein levels declined. The C/EBPβ-LIP protein steady-state level decreased considerably stronger than the C/EBPβ-LAP level and the C/EBPβ-LIP half-life was significantly shorter than the C/EBPβ-LAP half-life. The turn-over of both C/EBPβ-isoforms was regulated by ubiquitin/proteasome-dependent degradation. These data suggest that the protein stability of the C/EBPβ-isoforms is differentially regulated in the course of adipogenesis and in immature adipocytes. Constitutive overexpression of C/EBPβ-LIP had antiadipogenic activity in human ASC. C/EBPβ-LAP, which promotes adipogenesis in mouse 3T3-L1 preadipocytes by directly activating expression of the adipogenic keyregulator PPARγ2, induced the expression of PPARγ2 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/EBPβ-LAP led to reduced expression of PPARγ2 and FABP4, C/EBPα 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/EBPβ-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/EBPβ gene expression and C/EBPβ-LIP and C/EBPβ-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. SN - 1432-0436 UR - https://www.unboundmedicine.com/medline/citation/23314288/Role_of_C/EBPβ_LAP_and_C/EBPβ_LIP_in_early_adipogenic_differentiation_of_human_white_adipose_derived_progenitors_and_at_later_stages_in_immature_adipocytes_ DB - PRIME DP - Unbound Medicine ER -