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https://www.readbyqxmd.com/read/29576437/enterochromaffin-5-ht-cells-a-major-target-for-glp-1-and-gut-microbial-metabolites
#1
Mari L Lund, Kristoffer L Egerod, Maja S Engelstoft, Oksana Dmytriyeva, Elvar Theodorsson, Bhavik A Patel, Thue W Schwartz
OBJECTIVES: 5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear. METHODS AND RESULTS: TPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method...
March 10, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29524208/loss-of-ffar2-promotes-colon-cancer-by-epigenetic-dysregulation-of-inflammation-suppressors
#2
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/29494208/the-impact-of-short-chain-fatty-acids-on-glp-1-and-pyy-secretion-from-the-isolated-perfused-rat-colon
#3
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/29431874/short-chain-fatty-acids-induce-tissue-plasminogen-activator-in-airway-epithelial-cells-via-gpr41-43
#4
Yoshimasa Imoto, Atsushi Kato, Tetsuji Takabayashi, Masafumi Sakashita, James E Norton, Lydia A Suh, Roderick G Carter, Ava R Weibman, Kathryn E Hulse, Whitney Stevens, Kathleen E Harris, Anju T Peters, Leslie C Grammer, Bruce K Tan, Kevin Welch, David B Conley, Robert C Kern, Shigeharu Fujieda, Robert P Schleimer
BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on 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...
February 12, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29103715/effect-of-supplemental-yeast-culture-and-dietary-starch-content-on-rumen-fermentation-and-digestion-in-dairy-cows
#5
A L G Dias, J A Freitas, B Micai, R A Azevedo, L F Greco, J E P Santos
The objectives of this experiment were to evaluate the effect of feeding a culture of Saccharomyces cerevisiae on rumen metabolism and digestibility when cows are fed diets varying in starch content. Four lactating Holstein cows were assigned to a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Treatments were low starch (LS; 23% of diet DM) and no yeast culture (YC; LS-control), LS and 15 g of YC/d (LS-YC), high starch (HS; 29% of diet DM) and no YC (HS-control), and HS and 15 g of YC/d (HS-YC)...
January 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29049318/short-chain-fatty-acid-receptors-inhibit-invasive-phenotypes-in-breast-cancer-cells
#6
Madhumathi Thirunavukkarasan, Chao Wang, Angad Rao, Tatsuma Hind, Yuan Ru Teo, Abrar Al-Mahmood Siddiquee, Mohamed Ally Ibrahim Goghari, Alan Prem Kumar, Deron R Herr
Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are present in human plasma at micromolar concentrations. In addition to serving as metabolic precursors for lipid and carbohydrate synthesis, they also act as cognate ligands for two known G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. While there is evidence that these receptors may inhibit the progression of colorectal cancer, their roles in breast cancer cells are largely unknown. We evaluated the effects of enforced overexpression of these receptors in two phenotypically distinct breast cancer cell lines: MCF7 and MDA-MD-231...
2017: PloS One
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
#7
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
#8
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/28873082/ffar2-expression-regulates-leukaemic-cell-growth-in-vivo
#9
Laure B Bindels, Paolo E Porporato, Sarah Ducastel, Martina Sboarina, Audrey M Neyrinck, Evelyne M Dewulf, Olivier Feron, Sophie Lestavel, Patrice D Cani, Bart Staels, Pierre Sonveaux, Nathalie M Delzenne
BACKGROUND: Activation of free fatty acid receptor 2 (FFAR2) by microbiota-derived metabolites (e.g., propionate) reduces leukaemic cell proliferation in vitro. This study aims to test whether Ffar2 expression per se also influences leukaemia cell growth in vivo. METHODS: Bcr-Abl-expressing BaF cells were used as a leukaemia model and the role of Ffar2 was evaluated in Balb/c mice after lentiviral shRNA transduction. RESULTS: Our data formally establish that reduced leukaemic cell proliferation is associated with increased Ffar2 expression in vivo and in vitro...
October 24, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28622455/intestinal-metabolites-are-profoundly-altered-in-the-context-of-hla-b27-expression-and-functionally-modulate-disease-in-a-rat-model-of-spondyloarthritis
#10
Mark Asquith, Sean Davin, Patrick Stauffer, Claire Michell, Cathleen Janowitz, Phoebe Lin, Joe Ensign-Lewis, Jason M Kinchen, Dennis R Koop, James T Rosenbaum
OBJECTIVE: HLA-B27-associated spondyloarthritides are associated with an altered intestinal microbiota and bowel inflammation. We undertook this study to identify HLA-B27-dependent changes in both host and microbial metabolites in the HLA-B27/β2 -microglobulin (β2 m)-transgenic rat and to determine whether microbiota-derived metabolites could impact disease in this major model of spondyloarthritis. METHODS: Cecal contents were collected from Fischer 344 33-3 HLA-B27/β2 m-transgenic rats and wild-type controls at 6 weeks (before disease) and 16 weeks (with active bowel inflammation)...
October 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28552897/are-short-chain-fatty-acids-in-gut-microbiota-defensive-players-for-inflammation-and-atherosclerosis
#11
Hideo Ohira, Wao Tsutsui, Yoshio Fujioka
Intestinal flora (microbiota) have recently attracted attention among lipid and carbohydrate metabolism researchers. Microbiota metabolize resistant starches and dietary fibers through fermentation and decomposition, and provide short chain fatty acids (SCFAs) to the host. The major SCFAs acetates, propionate and butyrate, have different production ratios and physiological activities. Several receptors for SCFAs have been identified as the G-protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3), GPR43/FFAR2, GPR109A, and olfactory receptor 78, which are present in intestinal epithelial cells, immune cells, and adipocytes, despite their expression levels differing between tissues and cell types...
July 1, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28251760/the-nutrient-sensing-repertoires-of-mouse-enterochromaffin-cells-differ-between-duodenum-and-colon
#12
A M Martin, A L Lumsden, R L Young, C F Jessup, N J Spencer, D J Keating
BACKGROUND: Enterochromaffin (EC) cells within the gastrointestinal (GI) tract provide almost all body serotonin (5-hydroxytryptamine [5-HT]). Peripheral 5-HT, released from EC cells lining the gut wall, serves diverse physiological roles. These include modulating GI motility, bone formation, hepatic gluconeogenesis, thermogenesis, insulin resistance, and regulation of fat mass. Enterochromaffin cells are nutrient sensors, but which nutrients they are responsive to and how this changes in different parts of the GI tract are poorly understood...
June 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28131568/short-communication-free-fatty-acid-receptors-ffar1-and-ffar2-during-the-peripartal-period-in-liver-of-dairy-cows-grouped-by-their-postpartum-plasma-%C3%AE-hydroxybutyrate-concentrations
#13
M A Aguinaga Casañas, C T Schäff, E Albrecht, H M Hammon, B Kuhla, M Röntgen, G Nürnberg, M Mielenz
Free fatty acid receptors (FFAR) play significant roles in various physiological processes, including energy metabolism, through interaction with their ligands, fatty acids. To determine whether the receptors FFAR1 and FFAR2 are involved in the regulation of liver metabolism during the peripartal period, we selected 13 German Holstein multiparous dairy cows and grouped them as high β-hydroxybutyrate (H-BHB; n = 8) or low β-hydroxybutyrate (L-BHB; n = 5) according to their individual maximum plasma BHB concentration observed within wk 2 or 3 postpartum (H-BHB: >1 mmol/L and L-BHB: <0...
April 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28123937/fermentable-carbohydrate-stimulates-ffar2-dependent-colonic-pyy-cell-expansion-to-increase-satiety
#14
Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K Howard, Patrice D Cani, Amandine Everard, Michelle L Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D Bell, Kim Bell-Anderson, Charles R Mackay, Mohammad A Ghatei, Stephen R Bloom, Gary Frost, Gavin A Bewick
OBJECTIVE: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. METHODS: Wild-type or Ffar2 -/- mice were fed an inulin supplemented or control diet...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28070968/bacterial-short-chain-fatty-acid-metabolites-modulate-the-inflammatory-response-against-infectious-bacteria
#15
R O Corrêa, A Vieira, E M Sernaglia, M Lancellotti, A T Vieira, M J Avila-Campos, H G Rodrigues, M A R Vinolo
Short-chain fatty acids (SCFAs), predominantly acetic, propionic, and butyric acids, are bacterial metabolites with an important role in the maintenance of homeostasis due to their metabolic and immunomodulatory actions. Some evidence suggests that they may also be relevant during infections. Therefore, we aimed to investigate the effects of SCFAs in the effector functions of neutrophils to an opportunistic pathogenic bacterium, Aggregatibacter actinomycetemcomitans. Using a subcutaneous model to generate a mono, isolated infection of A...
January 9, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/27959892/ffa2-contribution-to-gestational-glucose-tolerance-is-not-disrupted-by-antibiotics
#16
Miles Fuller, Xiaoran Li, Robert Fisch, Moneb Bughara, Barton Wicksteed, Petia Kovatcheva-Datchary, Brian T Layden
During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis...
2016: PloS One
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
#17
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 (ApcMin/+ ). 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. ApcMin/+ and ApcMin/+ -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/27829484/invited-review-nutrient-sensing-receptors-for-free-fatty-acids-and-hydroxycarboxylic-acids-in-farm-animals
#18
REVIEW
M Mielenz
Data on nutrient sensing by free fatty acid receptors (FFAR1, FFAR2, FFAR3, FFAR4) and hydroxycarboxylic acid receptors (HCAR1, HCAR2) are increasing for human or rodent models. Both receptor families link intestinal fermentation by the microbiota and energy metabolism with cellular responses. Therefore, this finding provides a link that is independent of the only function of the fermentation products as energy substrates. For example, these reactions are associated with insulin secretion, regulation of lipolysis, adipose tissue differentiation and innate immune responses...
June 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27800650/supplementation-of-oligofructose-but-not-sucralose-decreases-high-fat-diet-induced-body-weight-gain-in-mice-independent-of-gustducin-mediated-gut-hormone-release
#19
Sandra Steensels, Leen Cools, Bert Avau, Laurien Vancleef, Ricard Farré, Kristin Verbeke, Inge Depoortere
SCOPE: Enteroendocrine cells sense nutrients through taste receptors similar to those on the tongue. Sweet and fatty acid taste receptors (FFAR) coupled to the gustatory G-protein, gustducin, on enteroendocrine cells play a role in gut hormone release. We studied if supplementation of artificial (sucralose) or prebiotic (oligofructose; OFS) sweeteners target gustducin-mediated signaling pathways to alter gut hormone release and reduce obesity-associated disorders. METHODS AND RESULTS: Wild-type (WT) and α-gustducin knockout (α-gust-/- ) mice were fed a high-fat diet and gavaged once daily (8 wk) with water or equisweet concentrations of sweeteners...
March 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27761989/the-diet-derived-short-chain-fatty-acid-propionate-improves-beta-cell-function-in-humans-and-stimulates-insulin-secretion-from-human-islets-in-vitro
#20
Attilio Pingitore, Edward S Chambers, Thomas Hill, Inmaculada Ruz Maldonado, Bo Liu, Gavin Bewick, Douglas J Morrison, Tom Preston, Gareth A Wallis, Catriona Tedford, Ramón Castañera González, Guo C Huang, Pratik Choudhary, Gary Frost, Shanta J Persaud
AIMS: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. MATERIALS AND METHODS: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon...
February 2017: Diabetes, Obesity & Metabolism
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