Regulation of the murine preadipocytes differentiation by bitter taste receptor Tas2r108 and Tas2r126

Taste 2 receptors (T2Rs) are known as receptors for sensing bitterness, but their gene expressions are observed in various extraoral tissues. T2Rs in adipocytes have attracted attention because bitter compounds influence lipid accumulation. However, the role of T2Rs in adipocytes has not been extensively investigated. This study investigated the functions of Tas2r108 and Tas2r126 in preadipocyte differentiation. Overexpression of Tas2r108 or Tas2r126 inhibited the differentiation of 3T3-L1 cells and mouse primary preadipocytes. Similarly, knockdown of Tas2r108 suppressed the differentiation of these cells. Consistent with the knockdown results, stimulation with T2R agonists during the differentiation of 3T3-L1 cells enhanced adipogenesis. Mechanistic analysis revealed that the suppressed differentiation by T2R overexpression involves the downregulation of Cebpb, while T2R knockdown involves the upregulation of Nr4a2 and Nr4a3 and downregulation of Egr2. Analysis with T2R agonists revealed that T2Rs in preadipocytes couple with inhibitory G-protein to downregulate intracellular cAMP concentrations, which works through ERK to enhance adipogenesis. These results demonstrate the regulation of adipocyte differentiation by T2Rs and suggest that bitter compounds enhance adipogenesis via T2Rs.