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https://www.readbyqxmd.com/read/28446062/metabolite-sensing-g-protein-coupled-receptors-facilitators-of-diet-related-immune-regulation
#1
Jian K Tan, Craig McKenzie, Eliana Mariño, Laurence Macia, Charles R Mackay
Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28322790/short-chain-fatty-acids-gpr41-and-gpr43-ligands-inhibit-tnf-%C3%AE-induced-mcp-1-expression-by-modulating-p38-and-jnk-signaling-pathways-in-human-renal-cortical-epithelial-cells
#2
Mamiko Kobayashi, Daisuke Mikami, Hideki Kimura, Kazuko Kamiyama, Yukie Morikawa, Seiji Yokoi, Kenji Kasuno, Naoki Takahashi, Takanobu Taniguchi, Masayuki Iwano
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced predominantly by gut microbiota fermentation of dietary fiber. SCFAs are newly identified as endogenous ligands of two orphan G protein-coupled receptors, GPR41 and GPR43, which have the potential to modulate inflammation. Therefore, GPR41 and GPR43 may mediate the link between the gut microbiome status and various disease conditions including renal inflammation. This study aimed at investigating whether SCFAs activate GPR41 and GPR43, and thereby exert anti-inflammatory effects in human renal cortical epithelial cells (HRCEs) as a main component of kidney tissue...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28241897/cloning-molecular-characterization-and-spatial-and-developmental-expression-analysis-of-gpr41-and-gpr43-genes-in-new-zealand-rabbits
#3
C Y Fu, L Liu, Q Gao, X Y Sui, F C Li
Short-chain fatty acids (SCFAs) play a regulatory role in various physiological processes in mammals and act as endogenous ligands for the G protein-coupled receptors (GPR) 41 and 43. The role of GPR41 and GPR43 in mediating SCFA signaling in the rabbit remains unclear. The present study was to investigate the sequence of the GPR41 and GPR43 messenger RNA (mRNA) and their expression pattern in different tissues and developmental stages in New Zealand rabbit. Comparison of genomic sequences in GenBank using the Basic Local Alignment Search Tool program suggested that the New Zealand rabbit GPR41 mRNA has high similarities with the human (84%), bovine (84%) and Capra hircus (84%) genes...
February 28, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28212864/gpr43-activation-enhances-psoriasis-like-inflammation-through-epidermal-upregulation-of-il-6-and-dual-oxidase-2-signaling-in-a-murine-model
#4
Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Ahmed M El-Sherbeeny, Mohammed M Al-Harbi, Talal S Almukhlafi
The gut is densely inhabited by commensal bacteria, which metabolize dietary fibers/undigested carbohydrates and produce short-chain fatty acids such as acetate. GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells. Acetate/GPR43 signaling has been shown to affect various inflammatory diseases through Th17 responses and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) generation. However, no study has previously explored the effects of GPR43 activation during psoriasis-like inflammation...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28075383/soluble-fibre-meal-challenge-reduces-airway-inflammation-and-expression-of-gpr43-and-gpr41-in-asthma
#5
Isabel Halnes, Katherine J Baines, Bronwyn S Berthon, Lesley K MacDonald-Wicks, Peter G Gibson, Lisa G Wood
Short chain fatty acids (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation-including changes in gene expression of free fatty acid receptors-in asthma. Adults with stable asthma consumed a soluble fibre meal (n = 17) containing 3...
January 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28049222/short-chain-fatty-acids-inhibit-oxidative-stress-and-inflammation-in-mesangial-cells-induced-by-high-glucose-and-lipopolysaccharide
#6
Wei Huang, Heng-Li Guo, Xian Deng, Ting-Ting Zhu, Jian-Feng Xiong, You-Hua Xu, Yong Xu
Recently, an connection between Short-chain fatty acids (SCFAs) produced by intestinal microbiota and kidney has been revealed. The aim of this study was to explore whether SCFAs or their specific G protein-coupled receptors 43 (GPR43) agonist inhibit oxidative stress and inflammatory response in glomerular mesangial cells (GMCs) induced by high glucose and lipopolysaccharide (LPS). Our research showed that treatment with SCFAs, especially acetate and butyrate, or GPR43 agonist significantly inhibited GMCs proliferation induced by high glucose and LPS, and then reversed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) but increased levels of antioxidant enzyme superoxide dismutase (SOD)...
February 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/27966553/microbiota-metabolite-short-chain-fatty-acid-acetate-promotes-intestinal-iga-response-to-microbiota-which-is-mediated-by-gpr43
#7
W Wu, M Sun, F Chen, A T Cao, H Liu, Y Zhao, X Huang, Y Xiao, S Yao, Q Zhao, Z Liu, Y Cong
Intestinal IgA, which is regulated by gut microbiota, has a crucial role in maintenance of intestinal homeostasis and in protecting the intestines from inflammation. However, the means by which microbiota promotes intestinal IgA responses remain unclear. Emerging evidence suggests that the host can sense gut bacterial metabolites in addition to pathogen-associated molecular patterns and that recognition of these small molecules influences host immune response in the intestines and beyond. We reported here that microbiota metabolite short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27892486/short-chain-fatty-acids-prevent-high-fat-diet-induced-obesity-in-mice-by-regulating-g-protein-coupled-receptors-and-gut-microbiota
#8
Yuanyuan Lu, Chaonan Fan, Ping Li, Yanfei Lu, Xuelian Chang, Kemin Qi
Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body weight may assist in the development of an effective weight control strategy. Dietary supplementation of acetate, propionate, butyrate or their admixture was shown to significantly inhibit the body weight gain induced by high-fat diet feeding. Supplementation of SCFAs caused significant changes in the expressions of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in the adipose tissue and reductions in the colon...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873088/anti-inflammatory-and-insulin-sensitizing-effects-of-free-fatty-acid-receptors
#9
Junki Miyamoto, Mayu Kasubuchi, Akira Nakajima, Ikuo Kimura
Chronic low-grade inflammation in macrophages and adipose tissues can promote the development of obesity and type 2 diabetes. Free fatty acids (FFAs) have important roles in various tissues, acting as both essential energy sources and signaling molecules. FFA receptors (FFARs) can modulate inflammation in various types of cells and tissues; however the underlying mechanisms mediating these effects are unclear. FFARs are activated by specific FFAs; for example, GPR40 and GPR120 are activated by medium and long chain FFAs, GPR41 and GPR43 are activated by short chain FFAs, and GPR84 is activated by medium-chain FFAs...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27866157/loss-of-free-fatty-acid-receptor-2-enhances-colonic-adenoma-development-and-reduces-the-chemopreventive-effects-of-black-raspberries-in-apcmin-mice
#10
Pan Pan, Chad W Skaer, Hsin-Tzu Wang, Kiyoko Oshima, Yi-Wen Huang, Jianhua Yu, Jianying Zhang, Martha M Yearsley, Kimberle A Agle, William R Drobyski, Xiao Chen, Li-Shu Wang
We previously showed that black raspberries (BRBs) have beneficial effects in human colorectal cancer and a mouse model of colorectal cancer (Apc(Min/+)). The current study investigated the role of free fatty acid receptor 2 (FFAR2) in colon carcinogenesis and whether the FFAR2 signaling pathway contributes to BRB-mediated chemoprevention in mice. FFAR2 (also named GPR43) is a member of the G-protein-coupled receptor family that is expressed in leukocytes and colon. Apc(Min/+) and Apc(Min/+)-FFAR2(-/-) mice were given a control diet or the control diet supplemented with 5% BRBs for 8 weeks...
January 2017: Carcinogenesis
https://www.readbyqxmd.com/read/27784876/diversity-of-the-intestinal-microbiota-differently-affects-non-neuronal-and-atropine-sensitive-ileal-contractile-responses-to-short-chain-fatty-acids-in-mice
#11
Masako Yajima, Shin-Ichiro Karaki, Takeshi Tsuruta, Shunsuke Kimura, Junko Nio-Kobayashi, Atsukazu Kuwahara, Takaji Yajima
Non-neuronal and atropine-sensitive ileal contractile responses to short chain fatty acids (SCFAs) are detected in the neonatal stage, and change with age or inflammatory conditions. However, the roles of luminal SCFAs in developmental changes have not yet been elucidated. We examined ileal contractile responses to SCFAs in mice colonized with different SCFA-producing intestinal microbiota under normal and inflammatory conditions. Using conventional (Conv), germ-free (GF), and gnotobiotic mice infected with Bifidobacterium (GB-bif), Propionibacterium (GB-prop), or Lactobacillus (GB-lact), ileal contractions were measured in 1-day-old neonates and 7-week-old mice using an isotonic transducer...
2016: Biomedical Research
https://www.readbyqxmd.com/read/27757764/application-of-gpcr-structures-for-modelling-of-free-fatty-acid-receptors
#12
Irina G Tikhonova
Five G protein-coupled receptors (GPCRs) have been identified to be activated by free fatty acids (FFA). Among them, FFA1 (GPR40) and FFA4 (GPR120) bind long-chain fatty acids, FFA2 (GPR43) and FFA3 (GPR41) bind short-chain fatty acids and GPR84 binds medium-chain fatty acids. Free fatty acid receptors have now emerged as potential targets for the treatment of diabetes, obesity and immune diseases. The recent progress in crystallography of GPCRs has now enabled the elucidation of the structure of FFA1 and provided reliable templates for homology modelling of other FFA receptors...
October 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27757760/ffa2-and-ffa3-in-metabolic-regulation
#13
Cong Tang, Stefan Offermanns
The short-chain fatty acid receptors FFA2 (GPR43) and FFA3 (GPR41) are activated by acetate, propionate, and butyrate. These ligands are produced by bacteria in the gut. In addition, the body itself can in particular produce acetate, and acetate plasma levels have been shown to be increased, e.g., in diabetic patients or during periods of starvation. FFA2 and FFA3 are both expressed by enteroendocrine cells and pancreatic β-cells. In addition, FFA2 is found on immune cells and adipocytes, whereas FFA3 is expressed by some peripheral neurons...
October 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27757758/ligands-at-the-free-fatty-acid-receptors-2-3-gpr43-gpr41
#14
Graeme Milligan, Daniele Bolognini, Eugenia Sergeev
A large number of reviews and commentaries have highlighted the potential role of the short-chain fatty acid receptors GPR41 (FFA3) and, particularly, GPR43 (FFA2) as an interface between the intestinal microbiota and metabolic and inflammatory disorders. However, short-chain fatty acids have very modest potency and display limited selectivity between these two receptors, and studies on receptor knockout mice have resulted in non-uniform conclusions; therefore, selective and high-potency/high-affinity synthetic ligands are required to further explore the contribution of these receptors to health and disease...
October 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27607913/development-of-novel-ligands-for-peptide-gpcrs
#15
REVIEW
Brian M Moran, Aine M McKillop, Finbarr Pm O'Harte
Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119)...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27562375/effects-of-a-treatment-with-se-rich-rice-flour-high-in-resistant-starch-on-enteric-dysbiosis-and%C3%A2-chronic-inflammation-in-diabetic-icr-mice
#16
Huaibo Yuan, Wenjuan Wang, Deyi Chen, Xiping Zhu, Lina Meng
BACKGROUND: Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). RESULTS: Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower...
May 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/27503855/the-neutrophil-response-induced-by-an-agonist-for-free-fatty-acid-receptor-2-gpr43-is-primed-by-tumor-necrosis-factor-alpha-and-by-receptor-uncoupling-from-the-cytoskeleton-but-attenuated-by-tissue-recruitment
#17
Lena Björkman, Jonas Mårtensson, Malene Winther, Michael Gabl, André Holdfeldt, Martin Uhrbom, Johan Bylund, Anders Højgaard Hansen, Sunil K Pandey, Trond Ulven, Huamei Forsman, Claes Dahlgren
Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca(2+), and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils...
October 15, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27449927/maternal-sodium-butyrate-supplement-elevates-the-lipolysis-in-adipose-tissue-and-leads-to-lipid-accumulation-in-offspring-liver-of-weaning-age-rats
#18
Jiabin Zhou, Shixing Gao, Jinglong Chen, Ruqian Zhao, Xiaojing Yang
BACKGROUND: Sodium butyrate (SB) is reported to regulate lipid metabolism in mammals, and the relationship between maternal nutrition and offspring growth has drawn much attention in the last several years. METHODS: To elucidate the effects of maternal dietary SB supplementation on hepatic lipid metabolism in weaning rats, we fed 16 primiparous purebred female SD rats either a chow-diet or a 1 % sodium butyrate diet throughout pregnancy and lactation. At weaning age, samples of the maternal subcutaneous adipose tissue and offspring liver were taken...
July 22, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27448578/microbiota-metabolite-short-chain-fatty-acids-gpcr-and-inflammatory-bowel-diseases
#19
REVIEW
Mingming Sun, Wei Wu, Zhanju Liu, Yingzi Cong
Gut microbiota has been well recognized in regulation of intestinal homeostasis and pathogenesis of inflammatory bowel diseases. However, the mechanisms involved are still not completely understood. Further, the components of the microbiota which are critically responsible for such effects are also largely unknown. Accumulating evidence suggests that, in addition to pathogen-associated molecular patterns, nutrition and bacterial metabolites might greatly impact the immune response in the gut and beyond. Short chain fatty acids (SCFA), which are metabolized by gut bacteria from otherwise indigestible fiber-rich diets, have been shown to ameliorate diseases in animal models of inflammatory bowel diseases (IBD) and allergic asthma...
January 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27348268/an-essential-role-of-ffar2-gpr43-in-dietary-fibre-mediated-promotion-of-healthy-composition-of-gut-microbiota-and-suppression-of-intestinal-carcinogenesis
#20
S Sivaprakasam, A Gurav, A V Paschall, G L Coe, K Chaudhary, Y Cai, R Kolhe, P Martin, D Browning, L Huang, H Shi, H Sifuentes, M Vijay-Kumar, S A Thompson, D H Munn, A Mellor, T L McGaha, P Shiao, C W Cutler, K Liu, V Ganapathy, H Li, N Singh
Composition of the gut microbiota has profound effects on intestinal carcinogenesis. Diet and host genetics play critical roles in shaping the composition of gut microbiota. Whether diet and host genes interact with each other to bring specific changes in gut microbiota that affect intestinal carcinogenesis is unknown. Ability of dietary fibre to specifically increase beneficial gut microbiota at the expense of pathogenic bacteria in vivo via unknown mechanism is an important process that suppresses intestinal inflammation and carcinogenesis...
June 27, 2016: Oncogenesis
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