Endocrine Abstracts

Brown adipose tissue (BAT) is key in energy homeostasis. Catecholamines are critically involved in the regulation of BAT-thermogenesis, yet current research has focussed on noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT-thermogenesis but the intracellular mechanisms have not been addressed. We applied our extensively characterised murine brown adipocyte cell line to address these questions.

D1-like and D2-like receptors were detectable at the protein level, as determined by immunoblotting. Treatment with DA caused an increase in cAMP levels. Oxygen consumption rates and uncoupling protein 1 levels increased, whereas the proton gradient at the inner mitochondrial membrane decreased after 24 h of DA-treatment. Mitochondrial mass (as determined by measurement of two mitochondrial proteins, TOMM20 and ATP synthase beta) also increased within this period of time. This was accompanied by an increase of PPAR gamma co-activator 1 alpha protein levels, a master regulator of mitochondrial mass. The D1-like receptor antagonist SCH 23390, but not the D2-like receptor antagonist Raclopride, abolished the DA-effect on the inner mitochondrial membrane potential (Delta Psi). Similar to DA, the specific D1-like receptor agonist SKF 38393 had an effect on Delta Psi after 24 h, whereas bromocriptine, a D2-like receptor agonist, had no significant effect. DA caused an increase of p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Delta Psi.

In summary, our study for the first reveals direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes.