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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-spondyloarthropathy
#1
Mark Asquith, Sean Davin, Patrick Stauffer, Claire Michell, Cathleen Janowitz, Phoebe Lin, Joe Ensign-Lewis, Jason M Kinchen, Dennis R Koop, Jim Rosenbaum
Objective HLA-B27 associated spondyloarthropathies are associated with an altered intestinal microbiota and bowel inflammation. Therefore, we sought to identify B27-dependent changes in both host and microbial metabolites in the HLA-B27/β2m rat and whether microbiota-derived metabolites could impact disease in this major model of spondyloarthropathy. Methods Cecal contents were collected from 6wk (pre-diseased) and 16wk (diseased) Fischer 344 HLA-B27/β2m transgenic rats and WT controls. Metabolomic profiling was performed by high-throughput gas- and liquid-chromatography-based mass spectrometry...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28552897/are-short-chain-fatty-acids-in-gut-microbiota-defensive-players-for-inflammation-and-atherosclerosis
#2
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...
May 27, 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
#3
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
#4
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%C3%A2-to%C3%A2-increase-satiety
#5
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
#6
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
#7
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
#8
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/27829484/invited-review-nutrient-sensing-receptors-for-free-fatty-acids-and-hydroxycarboxylic-acids-in-farm-animals
#9
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...
November 10, 2016: 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
#10
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
#11
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
https://www.readbyqxmd.com/read/27667443/human-and-mouse-monocytes-display-distinct-signalling-and-cytokine-profiles-upon-stimulation-with-ffar2-ffar3-short-chain-fatty-acid-receptor-agonists
#12
Zhiwei Ang, Jun Zhi Er, Nguan Soon Tan, Jinhua Lu, Yih-Cherng Liou, Johannes Grosse, Jeak Ling Ding
Knockout mice studies implicate the mammalian short-chain fatty acid (SCFA) receptors, FFAR2 and FFAR3- in colitis, arthritis and asthma. However, the correlation with human biology is uncertain. Here, we detected FFAR2 and FFAR3 expression in human monocytes via immunohistochemistry. Upon treatment with acetate SCFA or FFAR2- and FFAR3-specific synthetic agonists, human monocytes displayed elevated p38 phosphorylation and attenuated C5, CCL1, CCL2, GM-CSF, IL-1α, IL-1β and ICAM-1 inflammatory cytokine expression...
September 26, 2016: Scientific Reports
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
#13
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
https://www.readbyqxmd.com/read/27346602/the-neuropharmacology-of-butyrate-the-bread-and-butter-of-the-microbiota-gut-brain-axis
#14
REVIEW
Roman M Stilling, Marcel van de Wouw, Gerard Clarke, Catherine Stanton, Timothy G Dinan, John F Cryan
Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders...
October 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27324831/loss-of-free-fatty-acid-receptor-2-leads-to-impaired-islet-mass-and-beta-cell-survival
#15
Stephanie R Villa, Medha Priyadarshini, Miles H Fuller, Tanya Bhardwaj, Michael R Brodsky, Anthony R Angueira, Rockann E Mosser, Bethany A Carboneau, Sarah A Tersey, Helena Mancebo, Annette Gilchrist, Raghavendra G Mirmira, Maureen Gannon, Brian T Layden
The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs, and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate...
June 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27213723/vinegar-as-a-functional-ingredient-to-improve-postprandial-glycemic-control-human-intervention-findings-and-molecular-mechanisms
#16
REVIEW
Joseph Lim, Christiani Jeyakumar Henry, Sumanto Haldar
Type 2 diabetes prevalence worldwide is increasing and the burden is particularly high in Asian countries. Identification of functional food ingredients to curb the rise of diabetes among various Asian population groups is warranted. Vinegar is widely consumed throughout Asia, where the principle bioactive component is acetic acid. This review has collated data from human intervention trials to show that vinegar consumption seems more effective in modulating glycemic control in normal glucose-tolerant individuals than in either type 2 diabetics or in those with impaired glucose tolerance...
August 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27195116/regulation-of-immune-cell-function-by-short-chain-fatty-acids
#17
REVIEW
Renan Corrêa-Oliveira, José Luís Fachi, Aline Vieira, Fabio Takeo Sato, Marco Aurélio R Vinolo
Short-chain fatty acids (SCFAs) are bacterial fermentation products, which are chemically composed by a carboxylic acid moiety and a small hydrocarbon chain. Among them, acetic, propionic and butyric acids are the most studied, presenting, respectively, two, three and four carbons in their chemical structure. These metabolites are found in high concentrations in the intestinal tract, from where they are uptaken by intestinal epithelial cells (IECs). The SCFAs are partially used as a source of ATP by these cells...
April 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27186350/mechanisms-underlying-glucose-dependent-insulinotropic-polypeptide-and-glucagon-like-peptide-1-secretion
#18
REVIEW
Frank Reimann, Fiona M Gribble
The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1, are secreted from intestinal K- and L cells, respectively, with the former being most abundant in the proximal small intestine, whereas the latter increase in number towards the distal gut. Although an overlap between K- and L cells can be observed immunohistochemically or in murine models expressing fluorescent markers under the control of the two hormone promoters, the majority (>80%) of labeled cells seems to produce only one of these hormones...
April 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27016232/targeting-of-free-fatty-acid-receptor-1-in-eoc-a-novel-strategy-to-restrict-the-adipocyte-eoc-dependence
#19
Adnan Munkarah, Ismail Mert, Jasdeep Chhina, Suhail Hamid, Laila Poisson, Sharon Hensley-Alford, Shailendra Giri, Ramandeep Rattan
OBJECTIVES: Adipocyte derived free fatty acids (FFA) promote epithelial ovarian cancer (EOC) by acting as a fuel source to support the energy requirement of the cancer cells. FFA may also exert biological effects through signaling pathways. Recently, a family of FFA activated G-protein coupled receptors (FFAR/GPCRs) was identified. Our objective was to investigate the role of FFAR/GPCRs in EOC and assess their potential as therapeutic targets. METHODS: The mRNA (RT-PCR) expression of FFAR/GPCR family members (FFAR1/GPR40; FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120 and GPR84) was examined in: (1) a syngeneic mouse model of EOC fed high energy diet (60% fat) or regular diet (30% fat), (2) EOC cell lines exposed to free fatty acids and (3) specimens from 13 histologically normal ovaries and 28 high grade ovarian serous carcinomas...
April 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/26683635/selective-novel-inverse-agonists-for-human-gpr43-augment-glp-1-secretion
#20
Bi-Oh Park, Seong Heon Kim, Gye Yeong Kong, Da Hui Kim, Mi So Kwon, Su Ui Lee, Mun-Ock Kim, Sungchan Cho, Sangku Lee, Hyun-Jun Lee, Sang-Bae Han, Young Shin Kwak, Sung Bae Lee, Sunhong Kim
GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A-404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog...
January 15, 2016: European Journal of Pharmacology
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