Sensory signaling mediates the systemic metabolic and neurological effects of epigallocatechin gallate.

Background: Epigallocatechin gallate (EGCG), the primary green tea flavanol, is renowned for its diverse health benefits; however, its low systemic bioavailability presents a long-standing paradox in nutritional science. We hypothesized that EGCG exerts its physiological effects via oral chemosensory signaling pathways, independent of intestinal absorption. Methods: This study utilized wild-type and Skn-1a Results: Acute oral administration of EGCG or the bitter tastant denatonium benzoate significantly attenuated glycemic excursions and elevated plasma glucagon-like peptide-1 (GLP-1) levels in wild-type mice. Crucially, these effects were completely abolished in Skn-1a Conclusion: These findings indicate that EGCG acts as a "metabolic trigger" through Skn-1a-dependent chemosensory pathways, primarily involving T2R signaling. By demonstrating that bitter-related chemosensory signaling regulates systemic homeostasis and provides neuroprotective effects, this study supports a new concept of "sensory nutrition." This research positions gastrointestinal and oral chemosensors as a novel and non-invasive therapeutic target for managing metabolic syndrome and cognitive decline, overcoming the limitations of systemic bioavailability.