About this Research Topic
The increased prevalence in obesity and metabolic disease is a consequence of overconsumption of energy, fueled by changes in diet, and associated with changes of species within the microbiota and the metabolites they produce. Many of these metabolites activate members of the G protein-coupled receptor (GPCR) superfamily that represent the largest family of signaling receptors and the most successful therapeutic target. Their abundant and widespread expression, coupled with their huge potential to create pharmacological toolboxes, means they are an attractive target in any physiological tissue, including the gut and its communication with the central and enteric nervous systems, pancreas, adipose, and liver.
Our models of GPCR signaling have evolved over the past two decades. GPCRs can have multiple endogenous and synthetic ligands that could exhibit biased agonism. Furthermore, pleiotropy in cell signaling is also achieved by crosstalk of GPCR signaling mechanisms at a spatial and temporal level. However, the challenge is to understand how this evolved understanding of GPCR signaling can be applied to gut sensing of diverse metabolites and their distinct physiological and pathophysiological axes or pathways. Technological advances in the field, from chemogenetics, optogenetics, super-resolution imaging, and structural biology to patient organoids as in vitro ‘avatars’ and organ-on-chip systems, are opening opportunities to understand these complex cellular and physiological networks. Such approaches, in turn, could identify novel dietary and/or pharmacological interventions for a broad range of diseases.
This Research Topic aims to assemble original research articles, opinion papers, reviews, or commentaries that provide new information, or molecular and/or physiological insight into how pleiotropic GPCR signaling systems are integrated at the level of the gut and its communication with the brain and metabolic tissues. Topics that will be covered, but are not limited to, include:
-Crosstalk in GPCR signaling
-Novel tools to study GPCR signaling in these physiological systems
-Structural insight into nutrient-sensing or metabolic GPCRs
-Novel GPCR activity mechanisms in health and disease
-Application of 3D culture systems in GPCR signaling
Keywords: G protein-coupled Receptor, Signalling, Gut, Nutrient Sensing, Metabolism
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