Reduced IRS-2 and GLUT4 expression in PPARgamma2-induced adipocytes derived from C/EBPbeta and C/EBPdelta-deficient mouse embryonic fibroblasts.
In adipose tissue, the ability of cells to respond to insulin and to express genes such as those encoding fatty-acid-binding protein (422/aP2), lipoprotein lipase (LPL), adipsin and glucose transporter 4 (GLUT4) is acquired during their differentiation into mature adipocytes. It has been recognized that peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding proteins (C/EBPs) play critical roles in adipocyte differentiation. However, it remained uncertain whether PPARgamma or which C/EBP is involved in the acquisition of these characteristics. We introduced PPARgamma2 into C/EBPbeta/delta-double deficient mouse embryonic fibroblasts (MEFs), followed by stimulation with its ligands, in order to define the roles of C/EBPbeta and C/EBPdelta in phenotypic acquisition during adipocyte differentiation. This procedure resulted in differentiation of these MEFs into mature adipocytes morphologically similar to wild-type MEFs. However, the adipocytes derived from the C/EBPbeta/delta-deficient MEFs showed lower expression of GLUT4 and adipsin mRNA than those derived from wild-type MEFs, although aP2 and LPL mRNA levels were similar in both types. The C/EBPbeta/delta-deficient adipocytes also expressed lower amounts of insulin receptor substrate 2 (IRS-2) than the adipocytes derived from wild-type MEFs, whereas the amounts of insulin receptor and IRS-1 were similar. Finally, insulin-responsive 2-deoxyglucose uptake was lower in the C/EBPbeta/delta-deficient cells. It could thus be demonstrated that C/EBPbeta and C/EBPdelta are involved in the acquisition of IRS-2 and GLUT4 expression as well as in insulin-sensitive glucose uptake during adipocyte differentiation.
Yamamoto
Hiroyasu
H
Department of Molecular Medicine (C-4), Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Kurebayashi
Shogo
S
Hirose
Takahisa
T
Kouhara
Haruhiko
H
Kasayama
Soji
S
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495693:Slc2a4 protein, mouse; D014157:Transcription Factors; D011972:Receptor, Insulin