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For early hominids, frequent encounters with plant foods necessitated the ability to discern bitter poisons and adjust the activity of the gastrointestinal system in anticipation of carbohydrate-rich meals. Plants bitters were also used historically to manage a variety of metabolic and digestive disorders despite an immense structural diversity of bitter phytochemicals without a common molecular target. Our study confirms these observations in a standardized C57BL/6J prediabetic mouse model using 24 model compounds by demonstrating acute lower peak blood glucose values and improved glucose tolerance following intragastric, but not intraperitoneal, treatment. The administration of the synthetic bitter compound denatonium benzoate yielded similar results that were attenuated by co-application of the allosteric inhibitor of the bitter TAS2R receptors. We also show that these effects occur dose-dependently; associate with reduced glucose uptake, increased intracellular [Ca2+] fluxes, and enhanced GLP-1 expression; and are attenuated by the TAS2R inhibitor in the neuroendocrine STC-1 intestinal cells. These findings support the view that inhibition of glucose transport from the intestinal lumen to the blood by TAS2R bitter receptor signaling in the gut may represent a common mechanism in the acute response to oral ingestion of bitter phytochemicals. [ABSTRACT FROM AUTHOR]

The comfort food (CF) concept emerged during the latter half of the twentieth century. Although not well defined, CF can be described as familiar foods that elicit feelings of well-being and play a role in social interactions and psychological health. These foods are often calorically dense and nutrient-poor, and overconsumption of some CF may contribute to negative metabolic health outcomes. This is particularly relevant when considering the global increase in obesity, leading to the development of therapeutics for improved weight control and metabolic health. In this review, we aim to ( a ) provide a historical perspective of the CF concept, ( b ) detail some genetic, developmental, and cultural factors that determine food preference, ( c ) discuss the influence of diet on the gut-brain connection, hormones, nutrient absorption, and microbiome diversity, and ( d ) provide a perspective detailing possible future directions in which food technology may enable a new generation of CF with enhanced palatability and nutrient profiles while contributing to well-being and environmental sustainability.