Коротколанцюгові жирні кислоти: роль у порушеннях метаболізму
DOI:
https://doi.org/10.30978/MG-2021-2-55Ключові слова:
коротколанцюгові жирні кислоти, запалення, неалкогольна жирова хвороба печінки, ожиріння, цукровий діабетАнотація
Наведено дані досліджень щодо ролі коротколанцюгових жирних кислот у патогенезі механізму розвитку метаболічних порушень. Представлено коротку характеристику основних коротколанцюгових жирних кислот — ацетату, бутирату і пропіонату та зв’язок між їхнім виробленням та бактеріальними штамами кишкового мікробіому. Висвітлено дані щодо зміни вмісту ацетату, бутирату і пропіонату у фекаліях та крові залежно від маси тіла у тварин і людей. Детально викладено механізм використання зазначеними жирними кислотами таких сигнальних шляхів, як взаємодія з рецепторами жирних кислот FFA2 і FFA3, інгібування гістонових деацетилаз, для впливу на різні метаболічні процеси та енергетичний обмін. Описано їхню дію на глюкагоноподібний пептид‑1 (GLP‑1) і пептид YY унаслідок взаємодії з ентероендокринними L‑клітинами кишечника, що впливає на апетит і, відповідно, на споживання їжі. Також висвітлено вплив основних коротколанцюгових жирних кислот на кишкову проникність, що має важливе значення для збільшення проникнення ліпополісахариду грамнегативних бактерій з кишечника в кровообіг. Зазначено важливу роль коротколанцюгових жирних кислот у розвитку запальних процесів, наприклад, у запаленні низької градації, характерному для метаболічноасоційованих захворювань. Наведено дані досліджень щодо ролі ацетату, бутирату і пропіонату при неалкогольній жировій хворобі печінки, цукровому діабеті 2 типу, артеріальній гіпертензії, атеросклерозі та ендотеліальної дисфункції. Представлено результати досліджень як на тваринах, так і на людях, із безпосереднім уведення ацетату, бутирату і пропіонату. Описано чинники, які сприяють посиленню їхнього вироблення для впливу на метаболічні та запальні процеси.
Посилання
Adachi K, Sugiyama T, Yamaguchi Y et al. Gut microbiota disorders cause type 2 diabetes mellitus and homeostatic disturbances in gut-related metabolism in Japanese subjects. J Clin Biochem Nutr. 2019;64:231-238. doi: 10.3164/jcbn.18-101.
Adams SH, Hoppel CL, Lok KH et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr. 2009;139:1073-1081. doi: 10.3945/jn.108.103754.
Aisenberg WH, Huang J, Zhu W et al. Defining an olfactory receptor function in airway smooth muscle cells. Sci Rep. 2016;6:38231. doi.org/10.1038/srep38231.
Al-Lahham SH, Roelofsen H, Priebe M et al. Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest. 2010;40(5):401-407. doi: 10.1111/j.1365-2362.2010.02278.x.
Ali A, Boutjdir M, Aromolaran AS. Cardiolipotoxicity, inflammation, and arrhythmias: Role for Interleukin-6 molecular mechanisms. Front Physiol. 2018;9:1866. doi: 10.3389/fphys.2018.01866.
Amaretti A, Bernardi T, Tamburini E et al. Kinetics and metabolism of Bifidobacterium adolescentis MB 239 growing on glucose, galactose, lactose, and galactooligosaccharides. Appl Environ Microbiol. 2007;73:3637-3644. doi: 10.1128/AEM.02914-06.
Anastasovska J, Arora T, Canon GJ.S. et al. Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. Obesity. 2012;20(5):1016-1023. doi: 10.1038/oby.2012.6.
Ang Z, Er JZ, Tan NS et al. DingHuman and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists. Sci Rep. 2016;6:34145. doi: 10.1038/srep34145.
Aoyama M, Kotani J, Usami M. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways. Nutrition. 2010;26(6):653-61. doi: 10.1016/j.nut.2009.07.006.
Arantes RM, Nogueira AM. Distribution of enteroglucagon- and peptide YY-immunoreactive cells in the intestinal mucosa of germ-free and conventional mice. Cell Tissue Res. 1997;290:61-69. doi: 10.1007/s004410050908.
Archer BJ, Johnson SK, Devereux HM, Baxter AL. Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br J Nutr. 2004;91:591-599.
Arora T, Loo RL, Anastasovska J et al. Differential effects of two fermentable carbohydrates on central appetite regulation and body composition. PLoS One. 2012;7(8):e43263. doi: 10.1371/journal.pone.0043263.
Arora T, Sharma R, Frost G. Propionate. Anti-obesity and satiety enhancing factor?. Appetite. 2011;56:511-515. doi: 10.1016/j.appet.2011.01.
Asarat M, Vasiljevic T, Apostolopoulos V, Donkor O. Short-chain fatty acids regulate secretion of IL-8 from human intestinal epithelial cell lines in vitro. Immunol Invest. 2015;44(7):678-693. doi: 10.3109/08820139.2015.1085389.
Bailon E, Cueto-Sola M, Utrilla P et al. Butyrate in vitro immune-modulatory effects might be mediated through a proliferation-related induction of apoptosis. Immunobiology. 2010;215:863-873.
Baothman OA, Zamzami MA, Taher I et al. The role of Gut Microbiota in the development of obesity and Diabetes. Lipids Health Dis. 2016;15:108. doi: 10.1186/s12944-016-0278-4.
Barczynska R, Litwin M, Slizewska K et al. Bacterial Microbiota and Fatty Acids in the Faeces of Overweight and Obese Children. Pol J Microbiol. 2018;67:339-345. doi: 10.21307/pjm-2018-041.
Baugh ME, Steele CN, Angiletta CJ et al. Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes. Nutrients. 2018;10(6):793. doi: 10.3390/nu10060793.
Bellahcene M, O’Dowd JF, Wargent ET et al. Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content. Br J Nutr. 2013;109:1755-1764.
Benassi-Evans B, Clifton P, Noakes M, Fenech M. High-protein/high red meat and high-carbohydrate weight-loss diets do not differ in their effect on faecal water genotoxicity tested by use of the WIL2-NS cell line and with other biomarkers of bowel health. Mutat Res. 2010;703(2):130-6.
Bertocci LA, Jones JG, Malloy CR et al. Oxidation of lactate and acetate in rat skeletal muscle: Analysis by 13C-nuclear magnetic resonance spectroscopy. J Appl Physiol (Bethesda, Md, 1985). 1997;83:32-39. doi: 10.1152/jappl.1997.83.1.32.
Bindels LB, Walter J, Ramer-Tait AE. Resistant starches for the management of metabolic diseases. Curr Opin Clin Nutr Metab Care. 2015;18:559-565. doi: 10.1097/MCO.0000000000000223.
Blaut M. Gut microbiota and energy balance: Role in obesity. Proc Nutr Soc. 2015;74:227-234. doi: 10.1017/S0029665114001700.
Bloemen JG, Venema K, van de Poll MC. et al. Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin Nutr. 2009;28(6):657-661. doi: 10.1016/j.clnu.2009.05.011.
Boillot J, Alamowitch C, Berger A.-M. et al. Effects of dietary propionate on hepatic glucose production, whole-body glucose utilisation, carbohydrate and lipid metabolism in normal rats. Br J Nutr. 1995;73:241-251.
Bolognini D, Tobin AB, Milligan G, Moss CE. The pharmacology and function of receptors for short-chain fatty acids. Mol Pharmacol. 2016;89(3):388-98. doi: 10.1124/mol.115.102301.
Brighenti F, Castellani G, Benini L et al. Effect of neutralized and native vinegar on blood glucose and acetate responses to a mixed meal in healthy subjects. Eur J Clin Nutr. 1995;49:242-247.
Brinkworth GD, Noakes M, Clifton PM, Bird AR. Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Br J Nutr. 2009;101 (10):1493-502.
Brown AJ, Goldsworthy SM, Barnes AA et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312-11319.
Brusaferro A, Cozzali R, Orabona C et al. Is it time to use probiotics to prevent or treat obesity?. Nutrients. 2018;10:1613. doi: 10.3390/nu10111613.
Bucinskaite V, Tolessa T, Pedersen J et al. Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat. Neurogastroenterol Motil. 2009;21:978.
Byrne CS, Chambers ES, Alhabeeb H et al. Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods. Am J Clin Nutr. 2016;104(1):5-14. doi: 10.3945/ajcn.115.126706.
Byrne CS, Chambers ES, Morrison DJ, Frost G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes (Lond). 2015;39(9):1331-1338. doi: 10.1038/ijo.2015.84.
Canfora EE, van der Beek CM, Jocken JW.E. et al. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci Rep. 2017;7(1):2360. doi: 10.1038/s41598-017-02546-x.
Canfora EE, van der Beek CM, Hermes GD.A. et al. Supplementation of Diet with Galacto-oligosaccharides Increases Bifidobacteria, but not Insulin Sensitivity, in Obese Prediabetic Individuals. Gastroenterology. 2017;153:87-97. doi: 10.1053/j.gastro.2017.03.051. e3.
Canfora EE, Meex RC.R., Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019;15:261-273. doi: 10.1038/s41574-019-0156-z.
Cani PD, Bibiloni R, Knauf C et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470-1481. doi: 10.2337/db07-1403.
Cani PD, Dewever C, Delzenne NM. Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br J Nutr. 2004;92:521-526. doi: 10.1079/BJN20041225.
Cani PD, Joly E, Horsmans Y, Delzenne NM. Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr. 2006;60:567-572.
Cani PD, Neyrinck AM, Maton N, Delzenne NM. Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1. Obes Res. 2005;13:1000-1007.
Carpentier AC. Abnormal myocardial dietary fatty acid metabolism and diabetic cardiomyopathy. Can J Cardiol. 2018;34:605-614. doi: 10.1016/j.cjca.2017.12.029.
Cavaghan MK, Ehrmann DA, Polonsky KS. Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J Clin Investig. 2000;106:329-333. doi: 10.1172/JCI10761.
Chai JT, Digby JE, Choudhury RP. GPR109A and vascular inflammation. Curr Atheroscler Rep. 2013;15(5):352. doi: 10.1007/s11883-013-0325-9.
Chambers ES, Byrne CS, Aspey K et al. Acute oral sodium propionate supplementation raises resting energy expenditure and lipid oxidation in fasted humans. Diabetes Obes Metab. 2018;20(4):1034-1039. doi: 10.1111/dom.13159.
Chambers ES, Byrne CS, Rugyendo A et al. The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019;21(2):372-376. doi: 10.1111/dom.13500.
Chambers ES, Preston T, Frost G, Morrison DJ. Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health. Curr Nutr Rep. 2018;7(4):198-206. doi: 10.1007/s13668-018-0248-8.
Chambers ES, Viardot A, Psichas A et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64:1744-1754. doi: 10.1136/gutjnl-2014-307913.
Chang AJ, Ortega FE, Riegler J et al. Oxygen regulation of breathing through an olfactory receptor activated by lactate. Nature. 2015;527 (7577):240-244.
Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci, USA. 2014;111(6):2247-2252. doi: 10.1073/pnas.1322269111.
Ciarlo E, Savva A, Roger T. Epigenetics in sepsis: targeting histone deacetylases. Int J Antimicrob Agent. 2013;42 (suppl.):S8-12. doi: 10.1016/j.ijantimicag.2013.04.004.
Cornick S, Tawiah A, Chadee K. Roles and regulation of the mucus barrier in the gut. Tissue Barriers. 2015;3 (1-2):e982426. doi: 10.4161/21688370.2014.982426.
Corpeleijn E, Saris W, Blaak E. Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle. Obesity Reviews. 2009;10(2):178-193. doi: 10.1111/j.1467-789X.2008.00544.x.
Corrкa-Oliveira R, VieiraJosй LF.A., Sato FT, Vinolo MA.R. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol. ogy. 2016;5(4):e73. doi: 10.1038/cti.2016.17.
Cox MA, Jackson J, Stanton M et al. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E (2) and cytokines. World J Gastroenterol. 2009;15:5549-5557.
Damms-Machado A, Mitra S, Schollenberger AE et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int. 2015;2015:806248.
Dao MC, Everard A, Aron-Wisnewsky J et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65(3):426-36. doi: 10.1136/gutjnl-2014-308778.
Darzi J, Frost GS, Robertson MD. Effects of a novel propionate-rich sourdough bread on appetite and food intake. Eur J Clin Nutr. 2012;66(7):789-794. doi: 10.1038/ejcn.2012.1.
Daud NM, Ismail NA, Thomas EL et al. The impact of oligofructose on stimulation of gut hormones, appetite regulation, and adiposity. Obesity. 2014;22(6):1430-1438. doi: 10.1002/oby.20754.
De la Cuesta-Zuluaga J, Mueller NT, Alvarez-Quintero R et al. Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors. Nutrients. 2018;11:51. doi: 10.3390/nu11010051.
De Vadder F, Kovatcheva-Datchary P, Goncalves D et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156:84-96. doi: 10.1016/j.cell.2013.12.016.
Delaere F, Duchampt A, Mounien L et al. The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol Metab. 2013;2(1):47-53. doi: 10.1016/j.molmet.2012.11.003.
den Besten G, Bleeker A, Gerding A et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64(7):2398-2408. doi: 10.2337/db14-1213.
den Besten G, Lange K, Havinga R et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol. 2013;305:G900–G910.
den Besten G, van Eunen K, Groen AK et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54:2325-2340.
Didonna A, Opal P. The promise and perils of HDAC inhibitors in neurodegeneration. Ann Clin Transl Neurol. 2015;2(1):79-101. doi: 10.1002/acn3.147.
Digby JE, Martinez F, Jefferson A et al. Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms. Arterioscler Thromb Vasc Biol. 2012;32(3):669-76. doi: 10.1161/ATVBAHA.111.241836.
Ding ST, Smith EO, McNeel RL, Mersmann HJ. Modulation of porcine adipocyte beta-adrenergic receptors by hormones and butyrate. J Anim Sci. 2000;78:927-933. doi: 10.2527/2000.784927x.
Donohoe DR, Collins LB, Wali A et al. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 2012;48:612-626. doi: 10.1016/j.molcel.2012.08.033.
Duncan SH, Belenguer A, Holtrop G et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73(4):1073-8.
Engelstoft MS, Park WM, Sakata I et al. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol Metab. 2013;2:376-392. doi: 10.1016/j.molmet.2013.
Feng W, Wu Y, Chen G et al. Sodium butyrate attenuates diarrhea in weaned piglets and promotes tight junction protein expression in colon in a GPR109A-dependent manner. Cell Physiol Biochem. 2018;47(4):1617-1629. doi: 10.1159/000490981.
Ferchaud-Roucher V, Pouteau E, Piloquet H et al. Colonic fermentation from lactulose inhibits lipolysis in overweight subjects. Am J Physiol Endocrinol Metab. 2005;289:E716–E720. doi: 10.1152/ajpendo.00430.2004.
Fernandes J, Su W, Rahat-Rozenbloom S et al. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes. 2014;4:e121. doi: 10.1038/nutd.2014.23.
Ferolla SM, Couto CA, Costa-Silva L et al. Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. Nutrients. 2016;8(7):397. doi: 10.3390/nu8070397.
Flint HJ, Bayer EA, Rincon MT et al. Polysaccharide utilization by gut bacteria: Potential for new insights from genomic analysis. Nat Rev Microbiol. 2008;6:121-131. doi: 10.1038/nrmicro1817.
Freeland KR, Wilson C, Wolever T. Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects. Br J Nutr. 2010;103:82-90.
Freeland KR, Wolever TM. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2010;103:460-466. doi: 10.1017/S0007114509991863.
Frost G, Cai Z, Raven M et al. Effect of short chain fatty acids on the expression of free fatty acid receptor 2 (Ffar2), Ffar3 and early-stage adipogenesis. Nutr Diabetes. 2014;4:e128.
Frost G, Sleeth ML, Sahuri-Arisoylu M et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611. doi: 10.1038/ncomms4611.
Fushimi T, Sato Y. Effect of acetic acid feeding on the circadian changes in glycogen and metabolites of glucose and lipid in liver and skeletal muscle of rats. Br J Nutr. 2005;94:714-719. doi: 10.1079/BJN20051545.
Furusawa Y, Obata Y, Fukuda S et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446-450.
Gao Z, Yin J, Zhang J et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509-1517. doi: 10.2337/db08-1637.
Gelis L, Jovancevic N, Veitinger S et al. Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes. J Biol Chem. 2016;291 (34):17772-86.
Ghosh A, Gao L, Thakur A et al. Role of free fatty acids in endothelial dysfunction. J Biomed Sci. 2017;24:50. doi: 10.1186/s12929-017-0357-5.
Goffredo M, Mass K, Parks EJ et al. Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth. J Clin Endocrinol Metab. 2016;101:4367-4376. doi: 10.1210/jc.2016-1797.
Gomez-Arango LF, Barrett HL, McIntyre HD et al. Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension. 2016;68(4):974-981. doi: 10.1161/hypertensionaha.116.07910.
Gonzalez A, Krieg R, Massey HD et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant. 2019;34(5):783-794. doi: 10.1093/ndt/gfy238.
Gratz SW, Hazim S, Richardson AJ et al. Dietary carbohydrate rather than protein intake drives colonic microbial fermentation during weight loss. Eur J Nutr. 2018;57(1):1-12. doi: 10.1007/s00394-018-1629-x.
Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol. 2013;182:375-387. doi: 10.1016/j.ajpath.2012.10.014.
Han X, Song H, Wang Y et al. Sodium butyrate protects the intestinal barrier function in peritonitic mice. Int J Clin Exp Med. 2015;8(3):4000-4007.
Heiss CN, Olofsson LE. Gut Microbiota-Dependent Modulation of Energy Metabolism. J Innate Immun 2018;10(3):163-171. doi: 10.1159/000481519.
Henagan TM, Stefanska B, Fang Z et al. Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning. Br J Pharmacol. 2015;172 (11):2782-2798. doi: 10.1111/bph.13058.
Hong Y.-H., Nishimura Y, Hishikawa D et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology. 2005;146:5092-5099.
Hong J, Jia Y, Pan S et al. Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice. Oncotarget. 2016;7:56071-56082. doi: 10.18632/oncotarget.11267.
Hosseini A, Behrendt C, Regenhard P et al. Differential effects of propionate or β-hydroxybutyrate on genes related to energy balance and insulin sensitivity in bovine white adipose tissue explants from a subcutaneous and a visceral depot1. J Anim Physiol Anim Nutr. 2012;96:570-580.
Hu ED, Chen DZ, Wu JL et al. High fiber dietary and sodium butyrate attenuate experimental autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier. Cell Immunol. 2018;328:24-32. doi: 10.1016/j.cellimm.2018.03.003.
Hudson BD, Tikhonova IG, Pandey SK et al. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3. J Biol Chem. 2012;287:41195-41209.
Hume MP, Nicolucci AC, Reimer RA. Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial. Am J Clin Nutr. 2017;105(4):790-799. doi: 10.3945/ajcn.116.140947.
Ikezaki A, Hosoda H, Ito K et al. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes. 2002;51:3408-3411. doi: 10.2337/diabetes.51.12.3408.
Iraporda C, Errea A, Romanin DE et al. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology. 2015;220:1161-1169.
Isken F, Klaus S, Osterhoff M et al. Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J Nutr Biochem. 2010;21:278-284.
Itsuki-Yoneda A, Kimoto M, Tsuji H et al. Effect of a hypolipidemic drug, Di (2-ethylhexyl) phthalate, on mRNA-expression associated fatty acid and acetate metabolism in rat tissues. Biosci Biotechnol Biochem. 2007;71:414-420. doi: 10.1271/bbb.60478.
Jakobsdottir G, Xu J, Molin G et al. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS One. 2013;8:e80476.
Jia Y, Hong J, Li H et al. Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation-associated beta3 -adrenergic receptor activation in high-fat diet-induced obese mice. Exp Physiol. 2017;102(2):273-281. doi: 10.1113/ep086114.
Jin CJ, Sellmann C, Engstler AJ et al. Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH). Br J Nutr. 2015;114:1745-1755. doi: 10.1017/S0007114515003621.
Jumpertz R, Le DS, Turnbaugh PJ et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94:58-65. doi: 10.3945/ajcn.110.010132.
Karaki S, Tazoe H, Hayashi H et al. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J Mol Histol. 2008;39:135-142.
Kasubuchi M, Hasegawa S, Hiramatsu T et al. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7:2839-2849. doi: 10.3390/nu7042839.
Kelly CJ, Glover LE, Campbell EL et al. Fundamental role for HIF-1alpha in constitutive expression of human beta defensin-1. Mucosal Immunol 2013;6:1110-1118.
Kelly CJ, Zheng L, Campbell EL et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17(5):662-671. doi: 10.1016/j.chom.2015.03.005.
Keenan MJ, Zhou J, McCutcheon KL et al. Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat. Obesity (Silver Spring). 2006;14:1523-1534. doi: 10.1038/oby.2006.176.
Kendrick SF, O’Boyle G, Mann J et al. Acetate, the key modulator of inflammatory responses in acute alcoholic hepatitis. Hepatology. 2010;51(6):1988-97. doi: 10.1002/hep.23572.
Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016;254:124-134. doi: 10.1016/j.cbi.2016.06.007.
Kim HJ, Bae SC. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res. 2011;3(2):166-79.
Kim MH, Kang SG, Park JH et al. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013;145:396-406. e391–e310. doi: 10.1053/j.gastro.2013.04.056.
Kim S, Goel R, Kumar A et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132(6):701-718. doi: 10.1042/cs20180087.
Kimura I, Inoue D, Maeda T et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci USA. 2011;108:8030-8035.
Kimura I, Ozawa K, Inoue D et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829. doi: 10.1038/ncomms2852.
Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332-1345. doi: 10.1016/j.cell.2016.05.041.
Kondo T, Kishi M, Fushimi T, Kaga T. Acetic Acid Upregulates the Expression of Genes for Fatty Acid Oxidation Enzymes in Liver To Suppress Body Fat Accumulation. J Agric Food Chem. 2009;57:5982-5986. doi: 10.1021/jf900470c.
Krief S, Feve B, Baude B et al. Transcriptional modulation by n-butyric acid of beta 1-, beta 2-, and beta 3-adrenergic receptor balance in 3T3-F442A adipocytes. J Biol Chem. 1994;269(9):6664-6670.
Kroger J, Jacobs S, Jansen EH et al. Erythrocyte membrane fatty acid fluidity and risk of type 2 diabetes in the EPIC-Potsdam study. Diabetologia. 2015;58:282-289. doi: 10.1007/s00125-014-3421-7.
Laurent C, Simoneau C, Marks L et al. Effect of acetate and propionate on fasting hepatic glucose production in humans. Eur J Clin Nutr. 1995;49:484-491.
Layden BT, Angueira AR, Brodsky M et al. Short chain fatty acids and their receptors: New metabolic targets. Transl Res J Lab Clin Med. 2013;161:131-140. doi: 10.1016/j.trsl.2012.10.007.
Layden BT, Yalamanchi SK, Wolever TM et al. Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes Targets Ther. 2012;5:49-55. doi: 10.2147/DMSO.S29244.
Leeman M, Ostman E, Bjorck I. Vinegar dressing and cold storage of potatoes lowers postprandial glycaemic and insulinaemic responses in healthy subjects. Eur J Clin Nutr. 2005;59:1266-1271. doi: 10.1038/sj.ejcn.1602238.
Ley RE, Backhed F, Turnbaugh P et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102 (31):11070-5. doi: 10.1073/pnas.0504978102.
Li G, Yao W, Jiang H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. J Nutr. 2014;144 (12):1887-1895. doi: 10.3945/jn.114.198531.
Li L, Ma L, Fu P. Gut microbiota–derived short-chain fatty acids and kidney diseases. Drug Des Devel Ther. 2017;11:3531-3542. doi: 10.2147/DDDT.S150825.
Li Q, Wu T, Liu R et al. Soluble Dietary Fiber Reduces Trimethylamine Metabolism via Gut Microbiota and Co-Regulates Host AMPK Pathways. Molecular Nutrition & Food Research. 2017;61 (12):1700473. doi: 10.1002/mnfr.201700473.
Li X, Shimizu Y, Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci Microbiota Food Health. 2017;36(4):135-140. doi: 10.12938/bmfh.17-010.
Li X, Xu Q, Jiang T et al. A comparative study of the antidiabetic effects exerted by live and dead multi-strain probiotics in the type 2 diabetes model of mice. Food Funct. 2016;7:4851-4860. doi: 10.1039/C6FO01147K.
Li Z, Yi CX, Katiraei S et al. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit. Gut. 2018;67(7):1269-1279. doi: 10.1136/gutjnl-2017-314050.
Liatis S, Grammatikou S, Poulia KA et al. Vinegar reduces postprandial hyperglycaemia in patients with type II diabetes when added to a high, but not to a low, glycaemic index meal. Eur J Clin Nutr. 2010;64:727-732. doi: 10.1038/ejcn.2010.89.
Liljeberg H, Bjorck I. Delayed gastric emptying rate may explain improved glycaemia in healthy subjects to a starchy meal with added vinegar. Eur J Clin Nutr. 1998;52:368-371. doi: 10.1038/sj.ejcn.1600572.
Lim J, Henry CJ, Haldar S. Vinegar as a functional ingredient to improve postprandial glycemic control—Human intervention findings and molecular mechanisms. Mol Nutr Food Res. 2016;60:1837-1849. doi: 10.1002/mnfr.201600121.
Lin HV, Frassetto A, Kowalik EJ et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7:e35240. doi: 10.1371/journal.pone.0035240.
Liou AP, Paziuk M, Luevano JM et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178. doi: 10.1126/scitranslmed.3005687.
Liu L, Li L, Min J et al. Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells. Cell Immunol. 2012;277 (1-2):66-73. doi: 10.1016/j.cellimm.2012.05.011.
Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1-8. doi: 10.1111/j.1574-6968.2009.01514.x.
Lu Y, Fan C, Li P et al. Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci Rep. 2016;6:37589. doi: 10.1038/srep37589.
Lukovac S, Belzer C, Pellis L et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio. 2014;5(4):e01438-14. doi: 10.1128/mBio.01438-14.
Maa MC, Chang MY, Hsieh MY et al. Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity. J Nutr Biochem. 2010;21 (12):1186-1192. doi: 10.1016/j.jnutbio.2009.10.004.
Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003;62:67-72. doi: 10.1079/PNS2002207.
Macia L, Tan J, Vieira AT et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun. 2015;6:6734. doi: 10.1038/ncomms7734.
Marino E, Richards JL, McLeod KH et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18(5):552-562. doi: 10.1038/ni.3713.
Maruta H, Yoshimura Y, Araki A et al. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells. PLoS ONE. 2016;11:e0158055. doi: 10.1371/journal.pone.0158055.
Maslowski KM, Vieira AT, Ng A et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.
Massimino SP, McBurney MI, Field CJ et al. Fermentable Dietary Fiber Increases GLP-1 Secretion and Improves Glucose Homeostasis Despite Increased Intestinal Glucose Transport Capacity in Healthy Dogs. J Nutr. 1998;128:1786-1793. doi: 10.1093/jn/128.10.1786.
Masui R, Sasaki M, Funaki Y et al. G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells. Inflam Bowel Dis. 2013;19 (13):2848-2856. doi: 10.1097/01.MIB.0000435444.14860.ea.
Matheus VA, Monteiro LC.S., Oliveira RB et al. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Experimental Biology and Medicine. 2017;242 (12):1214-1226. doi: 10.1177/1535370217708188.
Mattace RG, Simeoli R, Russo R et al. Effects of sodium butyrate and its synthetic amide derivative on liver inflammation and glucose tolerance in an animal model of steatosis induced by high fat diet. PLoS ONE. 2013;8:e68626. doi: 10.1371/journal.pone.0068626.
Mayengbam S, Lambert JE, Parnell JA et al. Dietary fiber supplementation normalizes serum metabolites of adults with overweight/obesity in a 12-week randomized control trial. FASEB J. 2018;31:433.5.
McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients. 2017;9 (12):1348. doi: 10.3390/nu9121348.
McNeil NI. The contribution of the large intestine to energy supplies in man. Am J Clin Nutr. 1984;39:338-342. doi: 10.1093/ajcn/39.2.338.
McNelis JC, Lee YS, Mayoral R et al. GPR43 potentiates β-cell function in obesity. Diabetes. 2015;64:3203-3217. doi: 10.2337/db14-1938.
Meimandipour A, Hair-Bejo M, Shuhaimi M et al. Gastrointestinal tract morphological alteration by unpleasant physical treatment and modulating role of Lactobacillus in broilers. Br Poult Sci. 2010;51:52-59. doi: 10.1080/00071660903394455.
Mells JE, Anania FA. The role of gastrointestinal hormones in hepatic lipid metabolism. Semin Liver Dis. 2013;33(4):343-357. doi: 10.1055/s-0033-1358527.
Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic beta-cells: Mechanism and glucose dependence. Diabetes Obes Metab. 2013;15:15-27. doi: 10.1111/j.1463-1326.2012.01663.x.
Meneilly GS, Greig N, Tildesley H et al. Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care. 2003;26:2835-2841. doi: 10.2337/diacare.26.10.2835.
Mirmonsef P, Zariffard MR, Gilbert D et al. Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands. Am J Reprod Immunol. 2012;67(5):391-400. doi: 10.1111/j.1600-0897.2011.01089.x.
Mithieux G. Nutrient control of hunger by extrinsic gastrointestinal neurons. Trends Endocrinol Metab. 2013;24:378-384. doi: 10.1016/j.tem.2013.04.005.
Mitrou P, Petsiou E, Papakonstantinou E et al. The role of acetic acid on glucose uptake and blood flow rates in the skeletal muscle in humans with impaired glucose tolerance. Eur J Clin Nutr. 2015;69:734-739. doi: 10.1038/ejcn.2014.289.
Moens F, Weckx S, De Vuyst L. Bifidobacterial inulin-type fructan degradation capacity determines cross-feeding interactions between bifidobacteria and Faecalibacterium prausnitzii. Int J Food Microbiol. 2016;231:76-85. doi: 10.1016/j.ijfoodmicro.2016.05.015.
Morkl S, Lackner S, Meinitzer A et al. Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women. Eur. J Nutr. 2018. 57 (8):2985-2997. doi: 10.1007/s00394-018-1784-0.
Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189-200. doi: 10.1080/19490976.2015.1134082.
Murphy EF, Cotter PD, Healy S et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635-42.
Nakajima A, Nakatani A, Hasegawa S et al. The short chain fatty acid receptor GPR43 regulates inflammatory signals in adipose tissue M2-type macrophages. PLoS One. 2017;12(7):e0179696. doi: 10.1371/journal.pone.0179696.
Nakao C, Yamada E, Fukaya M et al. Effect of acetate on glycogen replenishment in liver and skeletal muscles after exhaustive swimming in rats. Scand J Med Sci Sports 2001;11:33-37. doi: 10.1034/j.1600-0838.2001.011001033.x.
Natarajan N, Hori D, Flavahan S et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics. 2016;48 (11):826-834. doi: 10.1152/physiolgenomics.00089.2016.
Neuhaus EM, Zhang W, Gelis L et al. Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. J Biol Chem. 2009;284 (24):16218-25.
Nicolucci AC, Hume MP, Martinez I et al. Prebiotics reduce body fat and Alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology. 2017;153(3):711-722. doi: 10.1053/j.gastro.2017.05.055.
Nilsson A, Johansson E, Ekstrцm L, Bjцrck I. Effects of a brown beans evening meal on metabolic risk markers and appetite regulating hormones at a subsequent standardized breakfast: a randomized cross-over study. PLoS One. 2013;8(4):e59985. doi: 10.1371/journal.pone.0059985.
Nilsson NE, Kotarsky K, Owman C, Olde B. Identification of a free fatty acid receptor, FFA 2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun. 2003;303:1047-1052.
Nilsson OL.A., Bilchik AJ, Goldenring JR et al. Distribution and immunocytochemical colocalization of peptide YY and enteroglucagon in endocrine cells of the rabbit colon. Endocrinology. 1991;129:139-148. doi: 10.1210/endo-129-1-139.
Nishimura S, Manabe I, Nagasaki M et al. CD8+-effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914-920. doi: 10.1038/nm.1964.
Nohr MK, Pedersen MH, Gille A et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154 (10):3552-3564. doi: 10.1210/en.2013-1142.
Ohira H, Fujioka Y, Katagiri C et al. Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages. J Atheroscler Thromb. 2013;20(5):425-442. doi: 10.5551/jat.15065.
Ostman E, Granfeldt Y, Persson L, Bjцrck I. Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects. Eur J Clin Nutr. 2005;59(9):983-988. doi: 10.1038/sj.ejcn.1602197.
Pagotto U, Gambineri A, Vicennati V et al. Plasma ghrelin, obesity, and the polycystic ovary syndrome: Correlation with insulin resistance and androgen levels. J Clin Endocrinol Metab. 2002;87:5625-5629. doi: 10.1210/jc.2002-020776.
Palomer X, Salvado L, Barroso E, Vazquez-Carrera M. An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int J Cardiol. 2013;168:3160-3172. doi: 10.1016/j.ijcard.2013.07.150.
Patrone V, Vajana E, Minuti A et al. Postoperative changes in fecal bacterial communities and fermentation products in obese patients undergoing bilio-intestinal bypass. Front Microbiol. 2016;7:200. doi: 10.3389/fmicb.2016.00200.
Park J, Goergen CJ, HogenEsch H, Kim CH. Chronically elevated levels of short-chain fatty acids induce T cell-mediated ureteritis and hydronephrosis. J Immunol. 2016;196(5):2388-2400. doi: 10.4049/jimmunol.1502046.
Park J, Kim M, Kang SG et al. Short chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2015;8:80-93. doi: 10.1038/mi.2014.44.
Parnell JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009;89:1751-1759 doi: 10.3945/ajcn.2009.27465.
Pedersen C, Lefevre S, Peters V et al. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study. Appetite. 2013;66:44-53 doi: 10.1016/j.appet.2013.02.017.
Perry RJ, Peng L, Barry NA et al. Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Nature. 2016;534:213-217. doi: 10.1038/nature18309.
Pessione E. Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. Front Cell Infect Microbiol. 2012;2:86. doi: 10.3389/fcimb.2012.00086.
Pilon M. Revisiting the membrane-centric view of diabetes. Lipids Health Dis. 2016;15:167. doi: 10.1186/s12944-016-0342-0.
Pilz S, Marz W. Free fatty acids as a cardiovascular risk factor. Clin Chem Lab Med. 2008;46:429-434. doi: 10.1515/CCLM.2008.118.
Pingitore A, Chambers ES, Hill T et al. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes Metab. 2017;19(2):257-265. doi: 10.1111/dom.12811.
Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5(2):202-7. doi: 10.4161/gmic.27492.
Pluznick J. Microbial short chain fatty acids and blood pressure regulation. Curr Hypertens Rep. 2017;19(4):25. doi: 10.1007/s11906-017-0722-5.
Pluznick JL, Protzko RJ, Gevorgyan H et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA. 2013;110 (11):4410-4415. doi: 10.1073/pnas.1215927110.
Priyadarshini M, Kotlo KU, Dudeja PK, Layden BT. Role of short chain fatty acid receptors in intestinal physiology and pathophysiology. Compr Physiol. 2018;8:1091-1115. doi: 10.1002/cphy.c170050.
Priyadarshini M, Villa SR, Fuller M et al. An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion. Mol Endocrinol. 2015;29:1055-1066. doi: 10.1210/me.2015-1007.
Psichas A, Sleeth M, Murphy K et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond). 2015;39(3):424-429. doi: 10.1038/ijo.2014.153.
Rafehi H, Lunke S, Kaspi A et al. Regulation of inflammatory gene expression by histone acetylation and HDAC inhibition in human aortic endothelial cells. Atherosclerosis. 2015;241(1):e6. doi: 10.1016/j.atherosclerosis.2015.04.038.
Rahat-Rozenbloom S, Fernandes J, Cheng J, Wolever TM.S. Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. Eur J Clin Nutr. 2016;71:953. doi: 10.1038/ejcn.2016.249.
Rahat-Rozenbloom S, Fernandes J, Cheng J et al. The acute effects of inulin and resistant-starch on postprandial serum short-chain fatty acids and second-meal glycaemic response in lean and overweight humans. Eur J Clin Nutr. 2017;71(2):227-233. doi: 10.1038/ejcn.2016.248.
Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TM. Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes. 2014;38:1525-1531. doi: 10.1038/ijo.2014.46.
Raqib R, Sarker P, Mily A et al. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial. BMC Infect Dis. 2012;12:111. doi: 10.1186/1471-2334-12-111.
Reimer RA, Willis HJ, Tunnicliffe JM et al. Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: A randomized controlled trial. Molecular Nutrition & Food Research. 2017;61 (11):1700484. doi: 10.1002/mnfr.201700484.
Riley LW, Raphael E, Faerstein E. Obesity in the United States — dysbiosis from exposure to low-dose antibiotics?. Front Public Health. 2013;1:69. doi: 10.3389/fpubh.2013.0006927.
Ríos-Covián D, Ruas-Madiedo P, Margolles A et al. Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Front Microbiol. 2016;7:185. doi: 10.3389/fmicb.2016.00185.
Riva A, Borgo F, Lassandro C et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2017;19:95-105. doi: 10.1111/1462-2920.13463.
Robertson MD, Bickerton AS, Dennis AL et al. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005;82:559-567. doi: 10.1093/ajcn/82.3.559.
Roshanravan N, Mahdavi R, Alizadeh E et al. Effect of butyrate and inulin supplementation on glycemic status, lipid profile and glucagon-like peptide 1 level in patients with type 2 diabetes: a randomized double-blind. Placebo-Controlled Trial Horm Metab Res. 2017;49 (11):886-891. doi: 10.1055/s-0043-119089.
Ross AB, Pere-Trépat E, Montoliu I et al. A whole-grain–rich diet reduces urinary excretion of markers of protein catabolism and gut microbiota metabolism in healthy men after one week. J Nutr. 2013;143(6):766-773. doi: 10.3945/jn.112.172197.
Russell WR, Gratz SW, Duncan SH et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr. 2011;93(5):1062-72.
Saeedi BJ, Kao DJ, Kitzenberg DA et al. HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell. 2015;26 (12):2252-2262. doi: 10.1091/mbc.E14-07-1194.
Sahuri-Arisoylu M, Brody LP, Parkinson JR et al. Reprogramming of hepatic fat accumulation and ‘browning’ of adipose tissue by the short-chain fatty acid acetate. Int J Obes (2005). 2016;40:955-963. doi: 10.1038/ijo.2016.23.
Saito H, Chi Q, Zhuang H et al. Odor coding by a Mammalian receptor repertoire. Sci Signal. 2009;2 (60):ra9. doi: 10.1126/scisignal.2000016.
Sakakibara S, Yamauchi T, Oshima Y et al. Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A (y) mice. Biochem Biophys Res Commun. 2006;344:597-604. doi: 10.1016/j.bbrc.2006.03.176.
Salazar N, Binetti A, Gueimonde M et al. Safety and intestinal microbiota modulation by the exopolysaccharide-producing strains Bifidobacterium animalis IPLA R1 and Bifidobacterium longum IPLA E44 orally administered to Wistar rats. Int J Food Microbiol. 2011;144:342-351. doi: 10.1016/j.ijfoodmicro.2010.10.016.
Samuel BS, Shaito A, Motoike T et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA. 2008;105:16767-16772.
Sano H, Nakamura E, Takahashi H, Terashima Y. Plasma insulin and glucagon responses to acute challenges of acetate, propionate, n-butyrate and glucose in growing gilts (Sus scrofa) Comp. Biochem Physiol A Physiol. 1995;110:375-378. doi: 10.1016/0300-9629 (94)00155-M.
Schaub A, Fьtterer A, Pfeffer K. PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily. Eur J Immunol. 2001;31 (12):3714-3725. doi: 10.1002/1521-4141 (200112)31 : 12<3714::aid-immu3714>3.0.co;2-1.
Schele E, Grahnemo L, Anesten F et al. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (GCG) and brain-derived neurotrophic factor (BDNF) in the central nervous system. Endocrinology. 2013;154 (10):3643-3651. doi: 10.1210/en.2012-2151.
Schilderink R, Verseijden C, de Jonge WJ. Dietary inhibitors of histone deacetylases in intestinal immunity and homeostasis. Front Immunol. 2013;4:226. doi: 10.3389/fimmu.2013.00226.
Schwiertz A, Taras D, Schafer K et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity. 2010;18:190-195. doi: 10.1038/oby.2009.167.
Secher A, Jelsing J, Baquero AF et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124:4473-4488.
Seljeset S, Siehler S. Receptor-specific regulation of ERK1/2 activation by members of the «free fatty acid receptor» family. J Recept Signal Transduct Res. 2012;32(4):196-201. doi: 10.3109/10799893.2012.692118.
Shang H, Sun J, Chen YQ. Clostridium Butyricum CGM CC0313.1 Modulates Lipid Profile, Insulin Resistance and Colon Homeostasis in Obese Mice. PLoS ONE. 2016;11:e0154373. doi: 10.1371/journal.pone.0154373.
Shi LZ, Wang R, Huang G et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208(7):1367-1376. doi: 10.1084/jem.20110278.
Singh A, Zapata RC, Pezeshki A et al. Inulin fiber dose-dependently modulates energy balance, glucose tolerance, gut microbiota, hormones and diet preference in high-fat-fed male rats. J Nutr. Biochem. 2018;59:142-152. doi: 10.1016/j.jnutbio.2018.05.017.
Singh N, Gurav A, Sivaprakasam S et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40(1):128-139. doi: 10.1016/j.immuni.2013.12.007.
Singh N, Thangaraju M, Prasad P et al. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J Biol Chem. 2010;285:27601-27608.
Smith PM, Howitt MR, Panikov N et al. The microbial metabolites, short-chain fatty acids, regulate colonic. Treg cell homeostasis Science. 2013;341 (6145):569-73. doi: 10.1126/science.1241165.
So D, Whelan K, Rossi M et al. Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis. Am J Clin Nutr. 2018;107(6):965-83. doi: 10.1093/ajcn/nqy041.
Soliman M, Kimura K, Ahmed M et al. Inverse regulation of leptin mRNA expression by short- and long-chain fatty acids in cultured bovine adipocytes. Domest Anim Endocrinol. 2007;33:400-409. doi: 10.1016/j.domaniend.2006.08.005.
Sowah SA, Riedl L, Damms-Machado A et al. Effects of Weight-Loss Interventions on Short-Chain Fatty Acid Concentrations in Blood and Feces of Adults: A Systematic Review. Adv Nutr. 2019;10(4):673-684. doi: 10.1093/advances/nmy125.
Suckow AT, Briscoe CP. Key questions for translation of FFA receptors: from pharmacology to medicines. Handb Exp Pharmacol. 2017;236:101-131. doi: 10.1007/164_2016_45.
Sun M, Wu W, Liu Z, Cong Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol. 2017;52(1):1-8. doi: 10.1007/s00535-016-1242-9.
Sunkara LT, Achanta M, Schreiber NB et al. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression. PLoS One. 2011;6:e27225.
Tang C, Ahmed K, Gille A et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21(2):173-177. doi: 10.1038/nm.3779.
Tedelind S, Westberg F, Kjerrulf M, Vidal A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: A study with relevance to inflammatory bowel disease. World J Gastroenterol. 2007;13:2826-2832. doi: 10.3748/wjg.v13.i20.2826.
Tiengo A, Valerio A, Molinari M et al. Effect of ethanol, acetaldehyde, and acetate on insulin and glucagon secretion in the perfused rat pancreas. Diabetes. 1981;30:705-709. doi: 10.2337/diab.30.9.705.
Tokarz VL, MacDonald PE, Klip A. The cell biology of systemic insulin function. J Cell Biol. 2018;217:2273-2289. doi: 10.1083/jcb.201802095.
Tolhurst G, Heffron H, Lam YS et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2. Diabetes. 2012;61:364-371.
Toscani A, Soprano DR, Soprano KJ. Sodium butyrate in combination with insulin or dexamethasone can terminally differentiate actively proliferating Swiss 3T3 cells into adipocytes. J Biol Chem. 1990;265:5722-5730.
Track NS, Cawkwell ME, Chin BC et al. Guar gum consumption in adolescent and adult rats: short-and long-term metabolic effects. Can J Physiol Pharmacol. 1985;63:1113-1121.
Turnbaugh PJ, Hamady M, Yatsunenko T et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480-487. doi: 10.1038/nature07540.
Turnbaugh PJ, Ley RE, Mahowald MA et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444 (7122):1027-31. doi: 10.1038/nature05414.
Van der Beek CM, Canfora EE, Lenaerts K et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016;130:2073-2082. doi: 10.1042/CS20160263.
van Dijk JW, Tummers K, Hamer HM, van Loon LJ. Vinegar co-ingestion does not improve oral glucose tolerance in patients with type 2 diabetes. J Diabetes Its Complicat. 2012;26:460-461. doi: 10.1016/j.jdiacomp.2012.05.009.
Veprik A, Laufer D, Weiss S et al. GPR41 modulates insulin secretion and gene expression in pancreatic β-cells and modifies metabolic homeostasis in fed and fasting states. FASEB J. 2016;30 (11):3860-3869. doi: 10.1096/fj.201500030R.
Vetrani C, Costabile G, Luongo D et al. Effects of whole-grain cereal foods on plasma short chain fatty acid concentrations in individuals with the metabolic syndrome. Nutrition. 2016;32(2):217-221. doi: 10.1016/j.nut.2015.08.006.
Vidrine K, Ye J, Martin RJ et al. Resistant starch from high amylose maize (HAM-RS2) and dietary butyrate reduce abdominal fat by a different apparent mechanism. Obesity (Silver Spring). 2014;22:344-348. doi: 10.1002/oby.20501.
Vinolo MA, Ferguson GJ, Kulkarni S et al. SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS ONE. 2011;6(6):e21205. doi: 10.1371/journal.pone.0021205.
Vinolo MA, Hirabara SM, Curi R. G-protein-coupled receptors as fat sensors. Curr Opin Clin Nutr Metab Care. 2012;15(2):112-116. doi: 10.1097/MCO.0b013e32834f4598.
Vinolo MA, Rodrigues HG, Hatanaka E et al. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem. 2011;22(9):849-855. doi: 10.1016/j.jnutbio.2010.07.009.
Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3 (10):858-76. doi: 10.3390/nu3100858.
Usami M, Kishimoto K, Ohata A et al. Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutr Res. 2008;28(5):321-8. doi: 10.1016/j.nutres.2008.02.012.
Wang L, Zhu Q, Lu A et al. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system. J Hypertens. 2017;35(9):1899-1908. doi: 10.1097/hjh.0000000000001378.
Wang X, He G, Peng Y et al. Sodium butyrate alleviates adipocyte inflammation by inhibiting NLR P3 pathway. Sci Rep. 2015;5:12676. doi: 10.1038/srep12676.
Weitkunat K, Schumann S, Nickel D et al. Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity. Mol Nutr Food Res. 2016;60:2611-2621. doi: 10.1002/mnfr.201600305.
Weitkunat K, Schumann S, Nickel D et al. Odd-chain fatty acids as a biomarker for dietary fiber intake: A novel pathway for endogenous production from propionate. Am J Clin Nutr. 2017;105:1544-1551. doi: 10.3945/ajcn.117.152702.
Weitkunat K, Stuhlmann C, Postel A et al. Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci Rep. 2017;7(1):6109. doi: 10.1038/s41598-017-06447-x.
Whitton C, Nicholson SK, Roberts C et al. National diet and nutrition survey: UK food consumption and nutrient intakes from the first year of the rolling programme and comparisons with previous surveys. Br J Nutr. 2011;106:1899-1914.
Wichmann A, Allahyar A, Greiner TU et al. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe. 2013;14:582-590. doi: 10.1016/j.chom.2013.09.012.
Windey K, De Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012;56:184-196. doi: 10.1002/mnfr.201100542.
Wolever TM, Fernandes J, Rao AV. Serum acetate:propionate ratio is related to serum cholesterol in men but not women. J Nutr. 1996;126:2790-2797. doi: 10.1093/jn/126.11.2790.
Wu J, Boström P, Sparks LM et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366-76. doi: 10.1016/j.cell.2012.05.016.
Xiong Y, Miyamoto N, Shibata K et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci USA. 2004;101:1045-1050. doi: 10.1073/pnas.2637002100.
Xu SS, Alam S, Margariti A. Epigenetics in vascular disease — therapeutic potential of new agents. Curr Vasc Pharmacol. 2014;12(1):77-86. doi: 10.2174/157016111201140327155551.
Yadav H, Lee JH, Lloyd J et al. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem. 2013;288:25088-25097. doi: 10.1074/jbc.M113.452516.
Yamashita H, Maruta H, Jozuka M et al. Effects of acetate on lipid metabolism in muscles and adipose tissues of type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem. 2009;73:570-576. doi: 10.1271/bbb.80634.
Yu X, Shahir AM, Sha J et al. Short-chain fatty acids from periodontal pathogens suppress histone deacetylases, EZH2, and SUV39H1 to promote Kaposi’s sarcoma-associated herpesvirus replication. J Virol. 2014;88(8):4466-79. doi: 10.1128/JVI.03326-13.
Zaibi MS, Stocker CJ, O’Dowd J et al. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett. 2010;584 (11):2381-2386. doi: 10.1016/j.febslet.2010.04.027.
Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: A parallel-group study. Lancet (Lond). 2002;359:824-830. doi: 10.1016/S0140-6736 (02)07952-7.
Zeng X, Sunkara LT, Jiang W et al. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs. PLoS ONE. 2013;8:e72922.
Zhang L, Du J, Yano N et al. Sodium Butyrate Protects-Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice. J Cell Biochem. 2017;8:2395-2408. doi: 10.1002/jcb.25902.
Zhao L, Zhang F, Ding X et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359:1151-1156. doi: 10.1126/science.aao5774.
Zhou D, Pan Q, Xin F.Zet al. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World J Gastroenterol. 2017;23(1):60-75. doi: 10.3748/wjg.v23.i1.60.
Zhou T, Chien MS, Kaleem S, Matsunami H. Single cell transcriptome analysis of mouse carotid body glomus cells. J Physiol. 2016;594 (15):4225-51. doi: 10.1113/JP271936.
Zydowo MM, Smolenski RT, Swierczynski J. Acetate-induced changes of adenine nucleotide levels in rat liver. Metab Clin Exp. 1993;42:644-648. doi: 10.1016/0026-0495 (93)90225-D.
