Nutrient sensing in the gut: interactions between chemosensory cells, visceral afferents and the secretion of satiation peptides

Abstract: The chemical environment of the intestinal lumen and the presence of nutrients in the gut result in the secretion of regulatory peptides and in the discharge of intestinal sensory afferent fibers. Since afferent nerve terminals do not directly extend into the intestinal lumen, their activation presumably depends on intermediary steps — post-absorptive mechanisms, i.e. direct neuronal activation by absorbed substances and pre-absorptive mechanisms, i.e. neuronal activation by a secondary substance released from the mucosal epithelium. Entero-endocrine cells (EEC) are able to ‘taste’ the luminal content and to function as chemosensory transducers to provide the interface between the intestinal lumen and the afferent nerve terminals. Their secretory products – mainly peptide hormones – are released upon stimulation by nutrients into the extracellular space of the lamina propria to either act 1) locally in a paracrine fashion to activate afferent terminals or other cells or 2) in an endocrine fashion via intestinal capillaries and the lymphatic system to bind to specific receptors at more distant targets. The chemosensory mechanisms by which EEC sense the intestinal lumen remain, however, poorly understood. Recent information suggest that taste signaling mechanisms known from the oral epithelium also operate in the mucosal epithelium. Several nutrient-responsive G-protein coupled receptors (GPCRs) have been identified in EEC including the sweet-taste responsive T1R2/T1R3 heterodimer or GPR120, responsive to free fatty acids (FFAs). This review provides a brief overview on gastrointestinal chemosensory mechanisms and their functional involvement in the secretion of satiation peptides with a focus on human studies albeit most evidence at present comes from in vitro or animal studies. [Copyright &y& Elsevier]