title: The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance.
abstract: The gastrointestinal tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural, and nutrient signals emanating from the gastrointestinal tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacologic and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing body weight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 highlights the therapeutic potential of gut-derived signals acting via nonphysiologic mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage gastrointestinal signals in order to treat obesity.
authors.affiliation: Clinical and Experimental Endocrinology, Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Portugal; Centre for Obesity Research, University College London, London, United Kingdom; University College London Hospitals Bariatric Centre for Weight Management and Metabolic Surgery, London, United Kingdom.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Monteiro
authors.affiliation: Centre for Obesity Research, University College London, London, United Kingdom; University College London Hospitals Bariatric Centre for Weight Management and Metabolic Surgery, London, United Kingdom; National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom. Electronic address: r.batterham@ucl.ac.uk.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Batterham
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000502:physiology; D054439:Ghrelin / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D020738:Leptin / Q000378:metabolism; D045265:Natriuretic Peptides / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009475:Neurons, Afferent; D009496:Neurotensin / Q000378:metabolism; D000080866:Nucleobindins; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D053772:Oxyntomodulin / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000098706:Taste Receptors, Type 2
chemical_list: D001054:Apolipoproteins A; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D020738:Leptin; D045265:Natriuretic Peptides; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D053772:Oxyntomodulin; D043562:Receptors, G-Protein-Coupled; C022205:apolipoprotein A-IV; C431926:taste receptors, type 1; D000098706:Taste Receptors, Type 2; D019894:Peptide YY; C072685:guanylin; C084362:uroguanylin; D009496:Neurotensin; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin
keywords: Enteroendocrine Cells; Gastrointestinal Peptides; Obesity