Aims/hypothesis  

Brown adipocytes provide a potentially important model system for understanding AMP-activated protein kinase (AMPK) regulation, where adrenergic stimulation leads to mitochondrial uncoupling through uncoupling protein-1 (UCP1) activity. AMPK is a sensor of energy homeostasis and has been implicated in glucose and lipid metabolism in several insulin-sensitive tissues. The aim of this study was to characterise the potential role of AMPK in adrenergically mediated glucose uptake and to find out whether UCP1 is involved in the adrenergic activation of AMPK.

Methods  

We used primary brown adipocytes differentiated in culture and measured AMPK phosphorylation and glucose uptake following adrenergic activation.

Results  

Treatment of adipocytes with noradrenaline (norepinephrine) caused phosphorylation of AMPK via -adrenoceptors and not ₁- or ₂-adrenoceptors. This effect was not ₃-adrenoceptor specific, since responses remained intact in adipocytes from ₃-adrenoceptor knock-out mice. These effects were also mimicked by forskolin and cAMP analogues. Treatment of cells with adenine 8--d-arabinofuranoside, an AMPK inhibitor, partially blocked -adrenoceptor-mediated increases in glucose uptake. Brown adipocytes are characterised by the production of UCP1, which can uncouple the mitochondria. Using adipocytes from Ucp1^+/+ and Ucp1^–/– mice, we showed that noradrenaline-mediated phosphorylation of AMPK does not require the presence or activity of UCP1.

Conclusions/interpretation  

These results suggest a pathway where increases in cAMP mediated by -adrenoceptors leads to activation of AMPK in brown adipocytes, which contributes in part to -adrenoceptor-mediated increases in glucose uptake, an effect independent of the presence or function of UCP1.