The Orphan G Protein-coupled Receptors GPR41 and GPR43 Are Activated by Propionate and Other Short Chain Carboxylic Acids
2003/03/01 by Andrew J. Brown, Susan M. Goldsworthy, Ashley Barnes +26 · 52 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · Immunology and Microbiology · #Receptor Mechanisms and Signaling #Neuropeptides and Animal Physiology #Immune Cell Function and Interaction
paper · pdf · doi:10.1074/jbc.m211609200
Abstract
GPR41 and GPR43 are related members of a homologous family of orphan G protein-coupled receptors that are tandemly encoded at a single chromosomal locus in both humans and mice. We identified the acetate anion as an agonist of human GPR43 during routine ligand bank screening in yeast. This activity was confirmed after transient transfection of GPR43 into mammalian cells using Ca(2+) mobilization and [(35)S]guanosine 5'-O-(3-thiotriphosphate) binding assays and by coexpression with GIRK G protein-regulated potassium channels in Xenopus laevis oocytes. Other short chain carboxylic acid anions such as formate, propionate, butyrate, and pentanoate also had agonist activity. GPR41 is related to GPR43 (52% similarity; 43% identity) and was activated by similar ligands but with differing specificity for carbon chain length, with pentanoate being the most potent agonist. A third family member, GPR42, is most likely a recent gene duplication of GPR41 and may be a pseudogene. GPR41 was expressed primarily in adipose tissue, whereas the highest levels of GPR43 were found in immune cells. The identity of the cognate physiological ligands for these receptors is not clear, although propionate is known to occur in vivo at high concentrations under certain pathophysiological conditions.
Cited by
- The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism
- Short-Chain Fatty Acids from Cutibacterium acnes Activate Both a Canonical and Epigenetic Inflammatory Response in Human Sebocytes
- Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis
- SCFA: mechanisms and functional importance in the gut
- The Microbiota-Gut-Brain Axis
- Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects
- Regulation of adipokine production in human adipose tissue by propionic acid
- The Gut–Brain Axis
- Immune Dysregulation in Branched Chain Organic Acidemias
- β-Hydroxybutyrate: A Signaling Metabolite
- Short‐chain fatty acids mediate gut microbiota–brain communication and protect the blood–brain barrier integrity
- Biocatalytical Acyl-Modification of Puerarin: Shape Gut Microbiota Profile and Improve Short Chain Fatty Acids Production in Rats
- From the gut to disease: Microbiota-derived short chain fatty acids and their precursors lactate and succinate in atherosclerosis and cancer
- FFAR2‐FFAR3 receptor heteromerization modulates short‐chain fatty acid sensing
- Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs
- Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases
- Cell free supernatants of Bifidobacterium adolescentis and Bifidobacterium longum suppress the tumor growth in colorectal cancer organoid model
- Potential role of microbes in antigen-based food sensitivities
- Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
- Cross-talk between microbiota–gut–brain axis and blood pressure regulation
- Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis
- Gut microbial metabolites link dietary history to appetite regulation
- Short-Chain Fatty Acid Receptors and Blood Pressure Regulation: Council on Hypertension Mid-Career Award for Research Excellence 2021
- The effect of short-chain fatty acids on M2 macrophages polarizationin vitroandin vivo
- Therapeutic potential of gut microbiota modulation in epilepsy: A focus on short-chain fatty acids
- GPR41 and GPR43 modulate rodent pancreatic α-cell function and growth
- Protonophore activity of short‐chain fatty acids induces their intracellular accumulation and acidification
- Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. [europepmc]
- Gut microbiome, obesity, and metabolic dysfunction. [europepmc]
- The microbiome in infectious disease and inflammation. [europepmc]
- Effects of gut microbes on nutrient absorption and energy regulation. [europepmc]
- Regulation of intestinal epithelial permeability by tight junctions. [europepmc]
- The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. [europepmc]
- Commensal bacteria at the interface of host metabolism and the immune system. [europepmc]
- β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. [europepmc]
- Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. [europepmc]
- Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. [europepmc]
- Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. [europepmc]
- Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. [europepmc]
- Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. [europepmc]
- Mechanisms and consequences of intestinal dysbiosis. [europepmc]
- Gut microbiota functions: metabolism of nutrients and other food components. [europepmc]
- Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System. [europepmc]
- β-Hydroxybutyrate: A Signaling Metabolite. [europepmc]
- Butyrate: A Double-Edged Sword for Health? [europepmc]
- Human gut microbiome: hopes, threats and promises. [europepmc]
- Metabolites as regulators of insulin sensitivity and metabolism. [europepmc]
- Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. [europepmc]
- Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. [europepmc]
- Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. [europepmc]
- Microbial short-chain fatty acids modulate CD8 + T cell responses and improve adoptive immunotherapy for cancer. [europepmc]
- Gut microbiome and health: mechanistic insights. [europepmc]
Related