Western Diet Downregulates Hepatic Bitter Taste Receptors: Potential Link to Altered Lipid Metabolism

Bitter taste receptors (TAS2Rs) beyond the oral cavity have gained increasing attention in recent years due to their expression in tissues and organs not traditionally linked to chemosensation, although their role in metabolism remains poorly understood. While the expression of TAS2Rs has been studied, the presence and function of these receptors in the liver are still unclear. Therefore, the aim of the present study was to assess whether a Western style diet regulates the mRNA and protein content of TAS2Rs' in mouse liver. Using both untargeted and targeted approaches, we analyzed the mRNA and protein content of bitter taste receptors in the liver and examined the potential correlation between TAS2Rs and cholesterol levels in the liver. We identified the mRNA of seven Tas2rs (Tas2r108, Tas2r120, Tas2r123, Tas2r130, Tas2r138, Tas2r143, and Tas2r144) in the liver of which the Tas2r138 mRNA and protein content was lower after 8 weeks on western diet, compared to control diet. Notably, the hepatic Tas2r138 mRNA level correlated positively with Srebf2 mRNA content as well as hepatic cholesterol and triglyceride levels. These findings suggest a potential regulatory link between Tas2rs and cholesterol, provide new insights into the roles of extra-oral bitter taste receptors and their possible regulation.