DIFFERENTIATION OF RAT BROWN ADIPOCYTES DURING LATE FETAL DEVELOPMENT- ROLE OF INSULIN-LIKE GROWTH-FACTOR-I

Rat brown adipocytes at day 22 of foetal development showed greater si ze, higher mitochondria content and larger amounts of lipids, as deter mined by flow cytometry, than 20-day foetal cells. Simultaneously, an inhibition on the percentage of brown adipocytes into S + G(2)/M phase s of the cell cycle was observed between days 20 and 22 of foetal deve lopment. The expression of several adipogenesis-related genes, such as fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase and insulin-regulated glucose transporter, increased at the end of foe tal life in brown adipose tissue. In addition, the lipogenic enzyme ac tivities and the lipogenic flux increased during late foetal developme nt, resulting in mature brown adipocytes showing a multilocular fat dr oplet phenotype. Concurrently, brown adipocytes induced the expression of the uncoupling protein (UP) mRNA and UP protein, as visualized by immunofluorescence. The three isoforms of CCAAT enhancer-binding prote ins (C/EBPs) were expressed at the mRNA level in brown adipose tissue at day 20. C/EBP alpha decreased and C/EBP beta and delta increased th eir expression between days 20 and 22 of foetal development, respectiv ely. Brown adipose tissue constitutively expressed insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) mRNAs. Moreover, IGF-IR mRNA content increased between days 20 and 22 in parallel with the occ urrence of tissue differentiation.