Small Phenolic Metabolites at the Nexus of Nutrient Transport and Energy Metabolism

Over time, human metabolism evolved to accommodate the challenges and benefits of plant foods that contain high amounts of carbohydrates and polyphenols. The latter are typically metabolized into small phenolic metabolites, including phenolic acids and their endogenous and microbial derivatives, that influence interconnected metabolic pathways involved in nutrient transport, energy metabolism, and neurotransmitter balance. Unlike other natural products, their biological effects arise from weak interactions with multiple molecular pathways rather than a single high-affinity receptor, making them versatile regulators of metabolic health. These compounds also modulate glucose transporters and carbohydrate metabolism, playing a crucial role in postprandial glucose and insulin responses. This review addresses the critical role of phenolic metabolites in metabolic health, with a focus on glucose homeostasis, insulin sensitivity, and carbohydrate metabolism. Incorporating polyphenols and phenolic acids into dietary strategies offers significant potential for improving insulin sensitivity, reducing metabolic disorder risks, and promoting whole-body glucose homeostasis. Furthermore, understanding how phenolic metabolites interact with metabolic pathways is essential for developing future effective nutritional strategies to support metabolic health.