title: Inhibition of 3T3-L1 adipocyte differentiation by expression of acyl-CoA-binding protein antisense RNA.
abstract: Several lines of evidence have recently underscored the significance of fatty acids or fatty acid-derived metabolites as signaling molecules in adipocyte differentiation. The acyl-CoA-binding protein (ACBP), which functions as an intracellular acyl-CoA pool former and transporter, is induced during adipocyte differentiation. In this report we describe the effects of expression of high levels of ACBP antisense RNA on the differentiation of 3T3-L1 cells. Pools of 3T3-L1 cells transfected with vectors expressing ACBP antisense RNA showed significantly less lipid accumulation as compared with cells transfected with the control vector. When individual clones were analyzed the degree of differentiation at day 10 was inversely correlated with the level of ACBP antisense RNA expression at day 0. Furthermore, in the clones with the highest levels of ACBP antisense expression, the induction of expression of the adipogenic transcription factors peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha as well as several adipocyte-specific genes was significantly delayed and reduced. The adipogenic potential of antisense-expressing cells was partially restored by transfection with a vector expressing high levels of ACBP. Taken together, these results are strong evidence that inhibition of differentiation is causally related to the decreased expression of ACBP, indicating that ACBP plays an important role during adipocyte differentiation.
authors.affiliation: Department of Molecular Biology, Odense University, Campusvej 55, DK-5230 Odense, Denmark. s.mandrup@molbiol.ou.dk
authors.forename: S
authors.initials: S
authors.lastname: Mandrup
authors.forename: R V
authors.initials: RV
authors.lastname: Sorensen
authors.forename: T
authors.initials: T
authors.lastname: Helledie
authors.forename: J
authors.initials: J
authors.lastname: Nohr
authors.forename: T
authors.initials: T
authors.lastname: Baldursson
authors.forename: C
authors.initials: C
authors.lastname: Gram
authors.forename: J
authors.initials: J
authors.lastname: Knudsen
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D026261:Diazepam Binding Inhibitor; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016372:RNA, Antisense / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D026261:Diazepam Binding Inhibitor; D007004:Hypoglycemic Agents; D007328:Insulin; D009687:Nuclear Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine