IGF-I induces the uncoupling protein gene expression in fetal rat brown adipocyte primary cultures: role of C/EBP transcription factors.
Fetal rat brown adipocytes proliferate and reach confluence when cultured in the presence of serum, almost losing their expression of the tissue-specific gene uncoupling protein (UCP). Confluent cells in a serum-free medium induced the expression of UCP in response to 1.4 nM IGF-I at 72 h, in a time-dependent manner. This effect was not produced by 1 nM insulin. However, insulin but not IGF-I induced the expression of the lipogenic marker malic enzyme, suggesting that IGF-I but not insulin is involved in the thermogenic differentiation process of fetal brown adipocytes. Furthermore, the expression of C/EBP transcription factors was present in fetal brown adipocytes prior culture, decreasing during cell proliferation throughout culture. After confluence, insulin induced the expression of C/EBP alpha and delta, whereas the expression of C/EBP beta remained essentially unmodified. IGF-I induced C/EBP alpha but decreased C/EBP delta, this might indicate that both transcription factors play a reciprocal role in the expression of the tissue specific UCP gene.
Guerra
C
C
Departamento de Bioquímica y Biología Molecular II, Centro Mixto C.S.I.C./U.C.M., Facultad de Farmacia, Ciudad Universitaria, Madrid, Spain.
Benito
M
M
Fernández
M
M
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007473:Ion Channels; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis*; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D000071256:Uncoupling Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D007334:Insulin-Like Growth Factor I; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating)