Silencing of dopamine receptor D5 inhibits the browning of 3T3-L1 adipocytes and ATP-consuming futile cycles in C2C12 muscle cells

As a part of the catecholamines, dopamine receptors (DRs) have not been extensively studied like β3-AR in the thermogenesis process. The present study investigates the effect of DRD5 in browning events and ATP-consuming futile cycles.siRNA technology, qPCR, immunoblot analysis, immunofluorescence, and staining methods were used to investigate the effect of DRD5 on 3T3-L1 and C2C12 cells.siDdr5 increased lipogenesis-associated effectors, and adipogenesis markers while reducing the expression of beige fat effectors. ATP-consuming futile cycle markers were also reduced following the siDrd5. On the contrary, pharmacological activation of DRD5 stimulated these effectors. Our mechanistic studies elucidated that DRD5 mediates fat browning via the cAMP-PKA-p38 MAPK signalling pathway in 3T3-L1 cells as well as the cAMP-SERCA-RyR pathway for the ATP-consuming futile cycles in both cells.siDrd5 positively regulates browning and ATP-consuming futile cycles, and understanding its functions will provide insights into novel strategies to treat obesity.