Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

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.

Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma

“…It is a key neurotransmitter in the hypothalamus and pituitary and secreted by specific neurons in a certain part of the brain ( 96 ). The DA receptor is a member of the G protein-coupled receptor family ( 97 , 98 ), which is divided into two families: D1-like receptors (D1 and D5) and D2-like receptors (D2, D3, and D4) ( 99 , 100 ). L-741626, a dopamine D2-like receptor antagonist, is expressed in airway smooth muscle and can relax ASM, which further indicates that dopamine D2-like receptor induces bronchiectasis by activating the intracellular cAMP signal pathway ( 101 ), while some researchers noticed that SCH23390, a dopamine D1-like receptor antagonist, had a contractile effect on the trachea and then found that there were DRD1 receptors in rat airway smooth muscle, which regulated tracheal relaxation through the cAMP signaling pathway ( 102 , 103 ).…”

Subcutaneous adipose tissue dopamine D2 receptor is increased in prediabetes and T2D

“…The expression of dopamine receptors in adipose tissue has been confirmed in both rodents and humans [ 15 , 16 ], and some dopamine actions have been studied [ 16 – 19 ]. However, the current knowledge of dopaminergic signaling in human adipose tissue in the context of obesity and T2D and its direct implications in adipose tissue metabolism is limited.…”

Anti-Inflammatory Effects of Peripheral Dopamine

“…D1-like receptors in brown adipocytes increase oxygen consumption rates and mitochondrial mass through p38 MAPK phosphorylation [ 96 ]. Nevertheless, the relevance of the effect of DA and its receptors on brown adipose tissue is still controversial, since the acute peripheral administration of a D1-like receptor agonist SKF38393 in mice only transiently increased brown tissue temperature after injection, while there was no sustained difference in temperature after repeated daily administration [ 97 ]. Moreover, these effects could be attributed to indirect consequences of DA receptors activation in the vascular system via peripheral action during administration of DA receptor agonists [ 98 ].…”