Alpha- and beta-adrenergic induction of the expression of the uncoupling protein thermogenin in brown adipocytes differentiated in culture.

In order to examine the control of expression of the gene coding for the brown fat specific uncoupling protein thermogenin (UCP), brown fat cells isolated as undifferentiated precursors from the interscapular brown adipose tissue of young mice were grown in culture. In these cells, it was possible by norepinephrine (NE) addition to induce specifically the expression of the UCP gene. The effect of NE was due to activation of transcription. The ability to express the UCP gene was maximal in cells around confluence; cell cultures younger or older than this showed a lower response. The response to NE showed a sharp optimum around 0.1 microM and was linear with time over the 4-h period studied. The presence of insulin or thyroid hormones facilitated the NE response. Pharmacological analysis of the adrenergic response indicated that UCP gene expression could be induced both via beta-receptors (probably beta 3) and via alpha 1-receptors; these effects were synergistic. It was concluded that it is possible to promote these precursor cells to advance to such a state of differentiation that they can demonstrate the selective feature of the brown fat cell, i.e. the ability to express UCP. The expression of the UCP gene is regulated via interacting adrenergic mechanisms.