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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
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
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
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)...
September 5, 2016: Current Opinion in Pharmacology
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...
August 26, 2016: Journal of the Science of Food and Agriculture
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
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...
2016: Lipids in Health and Disease
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...
July 23, 2016: Journal of Gastroenterology
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...
2016: Oncogenesis
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
Jian Tan, Craig McKenzie, Peter J Vuillermin, Gera Goverse, Carola G Vinuesa, Reina E Mebius, Laurence Macia, Charles R Mackay
The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC...
June 21, 2016: Cell Reports
K Y Chung, S B Smith, S H Choi, B J Johnson
We hypothesized that fatty acids would differentially affect G protein coupled receptor (GPR) 43 mRNA expression and GPR43 protein concentrations in bovine intramuscular (IM) and subcutaneous (SC) adipocytes. The GPR43 protein was detected in bovine liver, pancreas, and semimembranosus (MUS) muscle in samples taken at slaughter. Similarly, GPR43 protein levels were similar in IM adipose tissue and SM muscle but was barely detectable in SC adipose tissue. Primary cultures of IM and SC stromal vascular cells were isolated from bovine adipose tissues...
May 2016: Journal of Animal Science
Ronald Schilderink, Caroline Verseijden, Jurgen Seppen, Vanesa Muncan, Gijs R van den Brink, Tim T Lambers, Eric A van Tol, Wouter J de Jonge
In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA...
June 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sathish Sivaprakasam, Puttur D Prasad, Nagendra Singh
Epidemiological studies have linked increased incidence of inflammatory diseases and intestinal cancers in the developed parts of the world to the consumption of diets poor in dietary fibers and rich in refined carbohydrates. Gut bacteria residing in the intestinal lumen exclusively metabolize dietary fibers. Butyrate, propionate and acetate, which are collectively called short-chain fatty acids (SCFAs), are generated by fermentation of dietary fibers by gut microbiota. Evidences indicate that SCFAs are key players in regulating beneficial effect of dietary fibers and gut microbiota on our health...
August 2016: Pharmacology & Therapeutics
Junki Miyamoto, Sae Hasegawa, Mayu Kasubuchi, Atsuhiko Ichimura, Akira Nakajima, Ikuo Kimura
Excess energy is stored primarily as triglycerides, which are mobilized when demand for energy arises. Dysfunction of energy balance by excess food intake leads to metabolic diseases, such as obesity and diabetes. Free fatty acids (FFAs) provided by dietary fat are not only important nutrients, but also contribute key physiological functions via FFA receptor (FFAR)-mediated signaling molecules, which depend on FFAs' carbon chain length and the ligand specificity of the receptors. Functional analyses have revealed that FFARs are critical for metabolic functions, such as peptide hormone secretion and inflammation, and contribute to energy homeostasis...
2016: International Journal of Molecular Sciences
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
Jiamiao Hu, Ioannis Kyrou, Bee K Tan, Georgios K Dimitriadis, Manjunath Ramanjaneya, Gyanendra Tripathi, Vanlata Patel, Sean James, Mohamed Kawan, Jing Chen, Harpal S Randeva
Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis...
May 2016: Endocrinology
Seong Ho Choi, Sung Kwon Park, Chang Weon Choi, Xiang Zi Li, Kyoung Hoon Kim, Won Young Kim, Joon Jeong, Bradley J Johnson, Linsen Zan, Stephen B Smith
We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD) gene expression in subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control), with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments...
March 2016: Asian-Australasian Journal of Animal Sciences
Y Shi, Q Chen, Y Huang, L Ni, J Liu, J Jiang, N Li
AIM: The present study was designed to investigate the function and clinical implications of stool short-chain fatty acids (SCFAs) in patients with mixed refractory constipation. METHOD: Ascending colon specimens obtained from 30 patients with ascending colon cancer were regarded as the control group. Ascending colon specimens obtained from patients with mixed refractory constipation were regarded as the experimental group and were divided into three subgroups, according to Wexner scores [A constipation scoring system to simplify evaluation and management of constipated patients...
August 2016: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
Ying Hu, Richard K Le Leu, Claus T Christophersen, Roshini Somashekar, Michael A Conlon, Xing Q Meng, Jean M Winter, Richard J Woodman, Ross McKinnon, Graeme P Young
This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets...
April 2016: Carcinogenesis
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