Chronic dopamine D1 receptor activation does not alter brown fat thermogenesis

Energy homeostasis regulation represents a critical physiological process governing health and disease, with dysfunction contributing to the global obesity pandemic. Dopaminergic signaling has emerged as a key regulator of metabolic function through both central neural circuits and potential direct peripheral actions on metabolic tissues. However, comprehensive characterization of how sustained peripheral dopamine receptor activation affects whole-body metabolism and tissue-specific gene expression remains limited, particularly regarding the translation of promising in vitro thermogenic effects on brown and white adipocytes to chronic in vivo treatment scenarios. We administered dopamine or the dopamine D1 receptor agonist SKF-38393 via osmotic minipumps for one week in mice and assessed physiological parameters, tissue weights, and metabolic gene expression. Peripheral chronic dopamine D1 receptor activation did not affect body weight, food intake, and core as well as brown adipose tissue temperature across all groups. However, dopamine significantly increased the tail heat loss index, but brown and white adipose tissue showed no alterations in thermogenic marker expression. We also observed lower liver weight in the SKF treated group, accompanied by an upregulation of fatty acid synthase mRNA in both treatment groups compared to controls. This was not paralleled by significant changes in protein levels and other metabolic markers also remained stable. These findings demonstrate that chronic peripheral dopamine receptor activation produces tissue-specific responses, but does not affect peripheral thermogenic pathways. Our data suggest that the reported in vitro effects of dopamine on brown adipocytes are likely of minor biological relevance for thermogenesis in vivo.