Abstract
The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity.
Keywords: Fatty acids, amino acids, bile acids, G Protein-coupled receptors, enteroendocrine cells, gut hormones, cholecystokinin, glucagon-like peptide, metabotropic glutamate receptor, transgenic mice, obesity, diabetes, SGLT1, TIR2/TIR3
Current Medicinal Chemistry
Title: Recent Advances in Gut Nutrient Chemosensing
Volume: 19 Issue: 1
Author(s): C. A. Nguyen, Y. Akiba and J. D. Kaunitz
Affiliation:
Keywords: Fatty acids, amino acids, bile acids, G Protein-coupled receptors, enteroendocrine cells, gut hormones, cholecystokinin, glucagon-like peptide, metabotropic glutamate receptor, transgenic mice, obesity, diabetes, SGLT1, TIR2/TIR3
Abstract: The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity.
Export Options
About this article
Cite this article as:
A. Nguyen C., Akiba Y. and D. Kaunitz J., Recent Advances in Gut Nutrient Chemosensing, Current Medicinal Chemistry 2012; 19 (1) . https://dx.doi.org/10.2174/092986712803414033
DOI https://dx.doi.org/10.2174/092986712803414033 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Individual Differences in the Neurobiology of Social Stress: Implications for Depression-Cardiovascular Disease Comorbidity
Current Neuropharmacology Topics on Pharmacology for Dietitians in Modern Practice
Current Nutrition & Food Science Phosphate-Affinity Gel Electrophoresis Using a Phos-Tag Molecule for Phosphoproteome Study
Current Proteomics Update on Pharmacologic Retinal Vascular Toxicity
Current Pharmaceutical Design Treatment of Chronic Myeloid Leukemia Elderly Patients in the Tyrosine Kinase Inhibitor Era
Current Cancer Drug Targets Low Molecular Weight Compounds with Transition Metals as Free Radical Scavengers and Novel Therapeutic Agents
Cardiovascular & Hematological Agents in Medicinal Chemistry Dual Inhibitors of PI3K/mTOR or mTOR-Selective Inhibitors: Which Way Shall We Go?
Current Medicinal Chemistry Immunocal® and Preservation of Glutathione as a Novel Neuroprotective Strategy for Degenerative Disorders of the Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Photoelectrocatalytic Oxidation of Organics Under Visible Light Illumination: A Short Review
Current Organic Chemistry Phytochemistry and Pharmacological Update on Tetraterpenoids
The Natural Products Journal The Interplay of Marine Exposure in Gestational Diabetes
Current Women`s Health Reviews Food-Derived Peptides and Intestinal Functions
Current Pharmaceutical Design 1,4-Naphthoquinones and Other NADPH-Dependent Glutathione Reductase- Catalyzed Redox Cyclers as Antimalarial Agents
Current Pharmaceutical Design Rac-1 as a New Therapeutic Target in Cerebro- and Cardio-Vascular Diseases
Current Drug Targets Influence of ABCB1 Gene Polymorphisms and P-Glycoprotein Activity on Cyclosporine Pharmacokinetics in Peripheral Blood Mononuclear Cells in Healthy Volunteers
Drug Metabolism Letters New Vascular Disrupting Agents in Upper Gastrointestinal Malignancies
Current Medicinal Chemistry Synthesis of Medicinally Privileged Heterocycles through Dielectric Heating
Current Medicinal Chemistry Solid Lipid Nanoparticles: Promising Therapeutic Nanocarriers for Drug Delivery
Current Drug Delivery Status Epilepticus: An Overview
Current Drug Metabolism Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target
Current Cancer Therapy Reviews