Abstract
Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.
Highlights
Obesity and its metabolic consequences like type 2 diabetes have spread in recent years to become a worldwide pandemic[1,2]
To identify possible direct effects of dopamine receptor agonists on thermogenesis, we investigated mRNA expression of key thermogenic markers in interscapular Brown adipose tissue (BAT) tissue explants
In addition to the D1- and D2-agonist, we investigated dopamine itself to gather insight on the physiological effect of dopamine on interscapular BAT (iBAT) thermogenesis markers ex vivo
Summary
Obesity and its metabolic consequences like type 2 diabetes have spread in recent years to become a worldwide pandemic[1,2]. NE simultaneously binds to Gi-coupled α2-adrenergic receptors and inhibits AC activity, counteracting ADRB3mediated activation of BAT thermogenesis[17]. The purpose of this counter regulation is not understood to date, but underlines that endogenous neurotransmitter-receptor relationships are complex and not always s pecific[18,19,20]. The catecholamine neurotransmitter dopamine is the direct metabolic precursor of NE, binding to G-protein-coupled receptors[21,22]. Additional studies have shown that dopamine and the D1-agonist SKF38393 increase thermogenesis and mitochondrial mass of brown adipocytes in vitro[28]. That neither the D1-agonist, nor the D2-agonist have a sustained BAT-specific effect on thermogenesis upon direct application ex vivo or peripheral administration in vivo
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