Signal transduction in brown adipose tissue recruitment: noradrenaline and beyond

The classical effect of noradrenaline on brown adipose tissue is stimulation of heat production. However, it is likely that noradrenaline is also the major regulator of proliferation and differentiation. The adrenergic receptors involved include at least beta 1, beta 3, alpha 2 and alpha 1. Heat production is mainly stimulated via beta 3 receptors and cAMP. Cell proliferation is mainly stimulated via beta 1 receptors and cAMP. Cell differentiation is also adrenergically promoted; at least the expression of the gene for the tissue-specific uncoupling protein thermogenin is controlled via beta 3 receptors and cAMP. There is a switch in beta-receptor endowment between young (beta 1) and mature (beta 3) cells. The expression of several transcription factors is also under adrenergic control: c-Fos gene expression depends synergistically on beta- and alpha 1-stimulation mediated via cAMP and [Ca2+]i increases. C/EBP beta gene expression is regulated only via beta-receptors, but the expression of the C/EBP alpha gene shows a switch during differentiation: in young cells, the expression is represented through both beta- and alpha 1-receptors; in mature cells, the expression is stimulated via b-receptors. It is likely that noradrenaline exerts its proliferation- and differentiation-promoting action through alterations in the expression of these or other transcription factors.