Polyphenols are a diverse group of compounds that contribute to the flavor and health benefits of foods like green tea, berries, and dark chocolate. Among these compounds, flavonoids—responsible for the vibrant colors in fruits—have drawn attention due to their ability to interact with bitter taste receptors in the gut. These compounds are commonly ingested at a daily intake of 5 g and commonly associated with bitter taste.
Bitter taste receptors, like T2R46, are specialized proteins that detect bitter compounds. While they are primarily associated with taste perception on the tongue, these receptors are also present in the gastrointestinal tract, where they regulate hormone secretion and other vital functions. Researchers, led by Professor Naomi Osakabe, along with co-authors Takafumi Shimizu, Taiki Fushimi from the Shibaura Institute of Technology, and Vittorio Calabrese from the University of Catania, have realized that polyphenols activate T2R46 in the gut, triggering the release of glucagon-like peptide-1 (GLP-1), a hormone that plays a crucial role in regulating blood sugar levels. This study was made available online on November 5, 2024, and was published in Current Research in Food Science.
“Our findings show that polyphenols are more than just antioxidants—they are functional compounds capable of directly influencing gut hormone secretion,” says Professor Osakabe.
Prof. Osakabe also highlighted “Polyphenols are known to have cardiovascular disease prevention and cognitive function maintenance effects, but the mechanism behind these effects has remained a mystery for a long time. Therefore, we are focusing on the taste of polyphenols to elucidate their mechanism of action.”
To explore the interactions between polyphenols and T2R46, the team utilized advanced computational techniques, including in silico simulation techniques, which included molecular docking to predict how polyphenols bind to T2R46 and quantitative structure-activity relationship (QSAR) modeling to analyze the correlation between polyphenols structure and their binding strength to T2R46.
The simulations revealed that flavonoids exhibited the important binding interactions, facilitated by two critical amino acids in the receptor: W883.32 and E2657.39. These bonds, involving CH-π and salt bridge interactions, were essential for activating T2R46. Further QSAR analysis confirmed a strong correlation (R² = 0.9359) between polyphenol structures and their ability to bind to T2R46.
Flavonoids consistently outperformed other polyphenols and even non-polyphenolic bitter compounds, highlighting their unique role as activators of gut hormones. “These computational tools allowed us to uncover the structural secrets behind polyphenols’ ability to activate gut receptors,” explains Prof. Osakabe.
This research highlights the profound impact of polyphenol-rich diets on public health. Foods like citrus fruits, tea, and dark chocolate may naturally enhance gut hormone secretion, improving glucose tolerance and reducing the risk of metabolic disorders such as diabetes and obesity. “Our study bridges the gap between nutrition and medicine, showing how simple dietary changes can positively impact public health,” says Prof. Osakabe.
In addition to dietary recommendations, the findings offer a foundation for developing new therapies. Flavonoid-based compounds could be tailored to target T2R46, opening innovative treatment avenues for diabetes and obesity.
While the results are promising, the study emphasizes the need for further research to validate these findings in biological systems and explore the expression patterns and interactions between T2Rs, and how polyphenol-receptors influence them. With its focus on combining diet and technology, this research paves the way for healthier lifestyles and innovative medical solutions, offering hope for tackling chronic diseases through everyday foods.
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