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GPR43

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https://www.readbyqxmd.com/read/29689277/butyrate-ameliorated-nlrc3-protects-the-intestinal-barrier-in-a-gpr43-dependent-manner
#1
Di Cheng, Ji-Hao Xu, Jie-Yao Li, Si-Yi Wang, Ting-Feng Wu, Qi-Kui Chen, Tao Yu
BACKGROUND: Intestinal barrier dysfunctions are related to dysbacteriosis and chronic gut inflammation in type 2 diabetes. Although there is emerging evidence that the chronic gut inflammatory response is stimulated by nucleotide-binding oligomerization domain-like receptors (NLRs), the relationship and precise mechanism between NLRC3 and the colonic epithelial barrier remains largely elusive. METHODS: We investigated the function and mechanism of NLRC3 in the colonic tissues of diabetic mice and colonic epithelial cell lines...
April 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29644622/microbial-metabolites-short-chain-fatty-acids-restrain-tissue-bacterial-load-chronic-inflammation-and-associated-cancer-in-the-colon-of-mice
#2
Myunghoo Kim, Leon Friesen, Jeongho Park, Hyungjin M Kim, Chang H Kim
The intestinal immune system is regulated by microbes and their metabolites. The roles of gut microbial metabolites in regulating intestinal inflammation and tumorigenesis are incompletely understood. We systematically studied the roles of short-chain fatty acids (SCFAs) and their receptors (GPR43 or GPR41) in regulating tissue bacterial load, acute versus chronic inflammatory responses, and intestinal cancer development. SCFA receptor-, particularly GPR43-, deficient mice were defective in mounting appropriate acute immune responses to promote barrier immunity, and developed uncontrolled chronic inflammatory responses following epithelial damage...
April 12, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29569377/immune-regulation-by-microbiome-metabolites
#3
REVIEW
Chang H Kim
Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets...
March 22, 2018: Immunology
https://www.readbyqxmd.com/read/29544198/short-chain-fatty-acid-acetate-ameliorates-sepsis-induced-acute-kidney-injury-by-inhibition-of-nadph-oxidase-signaling-in-t-cells
#4
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29540664/prebiotic-attenuation-of-olanzapine-induced-weight-gain-in-rats-analysis-of-central-and-peripheral-biomarkers-and-gut-microbiota
#5
Amy Chia-Ching Kao, Sonia Spitzer, Daniel C Anthony, Belinda Lennox, Philip W J Burnet
Olanzapine is an effective antipsychotic drug but since it causes significant weight gain, it is not well tolerated by psychosis patients. The prebiotic, B-GOS® , attenuates metabolic dysfunction in obese subjects, and in rodents, alters central NMDA receptors and may affect serotonin receptors that are relevant in psychosis. We have determined whether B-GOS® influenced olanzapine-associated weight gain and central NMDA and serotonin receptors. Circulating acetate, IL-1β, IL-8 and TNFα, liver acetyl-CoA carboxylase (ACC), white adipose tissue (WAT) acetate receptor GPR43, and specific faecal bacteria genera were also measured to provide mechanistic information...
March 15, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29524208/loss-of-ffar2-promotes-colon-cancer-by-epigenetic-dysregulation-of-inflammation-suppressors
#6
Pan Pan, Kiyoko Oshima, Yi-Wen Huang, Kimberle A Agle, William R Drobyski, Xiao Chen, Jianying Zhang, Martha M Yearsley, Jianhua Yu, Li-Shu Wang
Free fatty acid receptor 2 (FFAR2, also named GPR43), is activated by short-chain fatty acids (SCFAs), such as butyrate, that are produced when gut bacteria ferment dietary fiber. FFAR2 has been suggested to regulate colonic inflammation, which is a major risk factor for the development of colon cancer and is also linked to epigenetic dysregulation in colon carcinogenesis. The current study assessed whether FFAR2, acting as an epigenetic regulator, protects against colon carcinogenesis. To mimic the mild inflammation that promotes human colon cancer, we treated mice with dextran sodium sulfate (DSS) overnight, which avoids excessive inflammation but induces mild inflammation that promotes colon carcinogenesis in the ApcMin/+ and the azoxymethane (AOM)-treated mice...
March 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29515566/the-metabolic-sensor-gpr43-receptor-plays-a-role-in-the-control-of-klebsiella-pneumoniae-infection-in-the-lung
#7
Izabela Galvão, Luciana P Tavares, Renan O Corrêa, José Luís Fachi, Vitor Melo Rocha, Marcela Rungue, Cristiana C Garcia, Geovanni Cassali, Caroline M Ferreira, Flaviano S Martins, Sergio C Oliveira, Charles R Mackay, Mauro M Teixeira, Marco Aurélio R Vinolo, Angélica T Vieira
Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29494208/the-impact-of-short-chain-fatty-acids-on-glp-1-and-pyy-secretion-from-the-isolated-perfused-rat-colon
#8
Charlotte Bayer Christiansen, Maria Buur Nordskov Gabe, Berit Svendsen, Lars Ove Dragsted, Mette Marie Rosenkilde, Jens J Holst
The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of GLP-1 and PYY secreting L-cells is of great interest because of the potential anti-diabetic and anti-obesity effects of GLP-1 and PYY. Short chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L-cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate and butyrate...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29477151/calcium-propionate-supplementation-improves-development-of-rumen-epithelium-in-calves-via-stimulating-g-protein-coupled-receptors
#9
X Z Zhang, W B Chen, X Wu, Y W Zhang, Y M Jiang, Q X Meng, Z M Zhou
In the present study, calcium propionate (CaP) was used as feed additive in the diet of calves to investigate their effects on rumen fermentation and the development of rumen epithelium in calves. To elucidate the mechanism in which CaP improves development of calf rumen epithelium via stimulating the messenger RNA (mRNA) expression of G protein-coupled receptors, a total of 54 male Jersey calves (age=7±1 days, BW=23.1±1.2 kg) were randomly divided into three treatment groups: control without CaP supplementation (Con), 5% CaP supplementation (5% CaP) and 10% CaP supplementation (10% CaP)...
February 26, 2018: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29431874/short-chain-fatty-acids-induce-tissue-plasminogen-activator-in-airway-epithelial-cells-via-gpr41-43
#10
Y Imoto, A Kato, T Takabayashi, M Sakashita, J E Norton, L A Suh, R G Carter, A R Weibman, K E Hulse, W Stevens, K E Harris, A T Peters, L C Grammer, B K Tan, K Welch, D B Conley, R C Kern, S Fujieda, R P Schleimer
BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs...
May 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29411774/gpr43-mediates-microbiota-metabolite-scfa-regulation-of-antimicrobial-peptide-expression-in-intestinal-epithelial-cells-via-activation-of-mtor-and-stat3
#11
Ye Zhao, Feidi Chen, Wei Wu, Mingming Sun, Anthony J Bilotta, Suxia Yao, Yi Xiao, Xiangsheng Huang, Tonyia D Eaves-Pyles, George Golovko, Yuriy Fofanov, Warren D'Souza, Qihong Zhao, Zhanju Liu, Yingzi Cong
The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIIIγ and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43-/- mice compared to that of wild-type (WT) mice...
February 7, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29353414/oral-administration-of-compound-probiotics-ameliorates-hfd-induced-gut-microbe-dysbiosis-and-chronic-metabolic-inflammation-via-the-g-protein-coupled-receptor-43-in-non-alcoholic-fatty-liver-disease-rats
#12
Yinji Liang, Shu Liang, Yupei Zhang, Yuanjun Deng, Yifang He, Yanning Chen, Chan Liu, Chenli Lin, Qinhe Yang
The aim of this study was to investigate how the effects of compound probiotics modulate the gut microbiota, short-chain fatty acid (SCFA), body composition, serum and liver lipids, and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) rats. Twenty-four male SD rats were randomly divided into 3 groups: normal control group (standard feed), high-fat diet (HFD) feeding group (83% standard feed + 10% lard oil + 1.5% cholesterol + 0.5% cholate + 5% sucrose), and compound probiotics intervention group (HFD + 0...
January 20, 2018: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/29338778/increased-whole-blood-ffa2-gpr43-receptor-expression-is-associated-with-increased-30-day-survival-in-patients-with-sepsis
#13
Zyad J Carr, Andry Van De Louw, Graham Fehr, Jialiu D Li, Allen Kunselman, Victor Ruiz-Velasco
OBJECTIVE: Sepsis is a condition associated with a dysregulated inflammatory response to infection with significant morbidity. Recent advances have elucidated the vital role that the short chain fatty acid glycoprotein receptor 43 (FFA2/GPR43) plays in inflammatory and immunomodulatory pathways. We hypothesized that elevated whole blood GPR43 RNA expression would be associated with increased 30-day survival in patients admitted with sepsis. Patients (n = 93) admitted to the intensive care unit with the diagnosis of sepsis underwent quantitative real time PCR within 48 h of intensive care unit admission...
January 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29311617/scfas-strongly-stimulate-pyy-production-in-human-enteroendocrine-cells
#14
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29276170/fiber-mediated-nourishment-of-gut-microbiota-protects-against-diet-induced-obesity-by-restoring-il-22-mediated-colonic-health
#15
Jun Zou, Benoit Chassaing, Vishal Singh, Michael Pellizzon, Matthew Ricci, Michael D Fythe, Matam Vijay Kumar, Andrew T Gewirtz
Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29198236/acetate-alters-the-process-of-lipid-metabolism-in-rabbits
#16
C Fu, L Liu, F Li
An experiment was conducted to investigate the effect of acetate treatment on lipid metabolism in rabbits. New Zealand Rabbits (30 days, n=80) randomly received a subcutaneous injection (2 ml/injection) of 0, 0.5, 1.0 or 2.0 g/kg per day body mass acetate (dissolved in saline) for 4 days. Our results showed that acetate induced a dose-dependent decrease in shoulder adipose (P0.05), acetate treatment significantly decreased the plasma adiponectin, insulin and triglyceride concentrations (P<0.05). In adipose, acetate injection significantly up-regulated the gene expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), differentiation-dependent factor 1 (ADD1), adipocyte protein 2 (aP2), carnitine palmitoyltransferase 1 (CPT1), CPT2, hormone-sensitive lipase (HSL), G protein-coupled receptor (GPR41), GPR43, adenosine monophosphate-activated protein kinase α1 (AMPKα1), adiponectin receptor (AdipoR1), AdipoR2 and leptin receptor...
December 4, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28992793/the-short-chain-fatty-acid-propionate-inhibits-adipogenic-differentiation-of-human-chorion-derived-mesenchymal-stem-cells-through-the-free-fatty-acid-receptor-2
#17
Judit Iván, Evelin Major, Adrienn Sipos, Katalin Kovács, Dániel Horváth, István Tamás, Péter Bay, Viktor Dombrádi, Beáta Lontay
Free fatty acid receptor 2 (FFAR2, also known as GPR43) is a G-protein-coupled receptor activated by short-chain fatty acids that are produced by gut microbiota through fermentation of nondigestible carbohydrates. FFAR2 functions as a metabolic sensor and is expressed in metabolically active tissues, such as adipose tissue. Earlier studies proved the connection between FFAR2 and adipocyte differentiation in mice. The aim of this study was to investigate the implication of FFAR2 receptor in adipogenesis in human chorion-derived mesenchymal stem cells (cMSCs)...
December 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28883043/ffar2-ffar3-receptor-heteromerization-modulates-short-chain-fatty-acid-sensing
#18
Zhiwei Ang, Ding Xiong, Min Wu, Jeak Ling Ding
Free fatty acid receptors 2 and 3 (FFAR2/FFA2/GPR43 and FFAR3/FFA3/GPR41) are mammalian receptors for gut microbiota-derived short-chain fatty acids (SCFAs). These receptors are promising drug targets for obesity, colitis, colon cancer, asthma, and arthritis. Here, we demonstrate that FFAR2 and FFAR3 interact to form a heteromer in primary human monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28843851/1-3-dichloro-2-propanol-induced-lipid-accumulation-in-hepg2-cells-through-camp-protein-kinase-a-and-amp-activated-protein-kinase-pathways-via-gi-o-coupled-receptors
#19
Jing Lu, Baochen Fang, Yiying Zheng, Xin Yu, Guoren Huang, Zhenning Wang, Xuming Deng, Shuang Guan
1,3-dichloro-2-propanol (1,3-DCP) is a food born hepatoxic chloropropanol contaminant that has been detected in a wide range of foods. In the present study, we investigated the effects and mechanisms of 1,3-DCP on lipid accumulation in HepG2 cells. The data showed 1,3-DCP significantly increased intracellular content of triglyceride (TG) and total cholesterol (TC) at 0.5-2μg/mL. Further results showed that 1,3-DCP greatly decreased cyclic AMP (cAMP) level. In addition, 1,3-DCP inhibited PKA and AMPK signaling pathway, but had no influence on intracellular calcium and regulated proteins...
July 27, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28796169/cell-surface-and-nuclear-receptors-in-the-colon-as-targets-for-bacterial-metabolites-and-its-relevance-to-colon-health
#20
REVIEW
Sathish Sivaprakasam, Yangzom D Bhutia, Sabarish Ramachandran, Vadivel Ganapathy
The symbiotic co-habitation of bacteria in the host colon is mutually beneficial to both partners. While the host provides the place and food for the bacteria to colonize and live, the bacteria in turn help the host in energy and nutritional homeostasis, development and maturation of the mucosal immune system, and protection against inflammation and carcinogenesis. In this review, we highlight the molecular mediators of the effective communication between the bacteria and the host, focusing on selective metabolites from the bacteria that serve as messengers to the host by acting through selective receptors in the host colon...
August 10, 2017: Nutrients
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