Abstract
Adipocyte differentiation is a well defined process that is under the control of transcriptional activators and repressors. We show that histone deacetylase (HDAC) inhibitors efficiently block adipocyte differentiation in vitro. This effect is specific to adipogenesis, as another mesenchymal differentiation process, osteoblastogenesis, is enhanced upon HDAC inhibition. Through the systematic genetic deletion of HDAC genes in cultured mesenchymal precursor cells, we show that deletion of HDAC1 and HDAC2 leads to reduced lipid accumulation, revealing redundant and requisite roles of these class I HDACs in adipogenesis. These findings unveil a previously unrecognized role for HDACs in the control of adipogenesis.
MeSH Terms
3T3-L1 Cells
Adipogenesis/drug effects,physiology
Animals
Biomarkers/metabolism
Blotting, Western
Butyrates/pharmacology
Cell Differentiation
Cells, Cultured
Embryo, Mammalian/cytology,drug effects,metabolism
Fibroblasts/cytology,drug effects,metabolism
Fluorescent Antibody Technique, Indirect
Gene Expression Profiling
Histone Deacetylase 1/antagonists & inhibitors,genetics,metabolism
Histone Deacetylase 2/antagonists & inhibitors,genetics,metabolism
Histone Deacetylase Inhibitors/pharmacology
Mesenchymal Stem Cells/cytology,drug effects,metabolism
Mice
Oligonucleotide Array Sequence Analysis
Osteogenesis
PPAR gamma/metabolism
RNA, Messenger/genetics,metabolism
Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Biomarkers
Butyrates
Histone Deacetylase Inhibitors
PPAR gamma
RNA, Messenger
Hdac1 protein, mouse
Hdac2 protein, mouse
Histone Deacetylase 1
Histone Deacetylase 2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Haberland Michael
Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Carrer Michele
Mokalled Mayssa H
Montgomery Rusty L
Olson Eric N
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