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.