Short-chain fatty acids in control of body weight and insulin sensitivity

Nature Reviews Endocrinology

Volumn 11, Issue 10, 2015, Pages 577-591

  Canfora, Emanuel E ^a   Jocken, Johan W ^a   Blaak, Ellen E ^a  

^a MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; BUTYRIC ACID; G PROTEIN COUPLED RECEPTOR; GLUCAGON LIKE PEPTIDE 1; INCRETIN; LEPTIN; PEPTIDE YY; SHORT CHAIN FATTY ACID; VOLATILE FATTY ACID;

ADIPOCYTE; ADIPOGENESIS; ADIPOSE TISSUE; CALORIC INTAKE; DIETARY FIBER; ENERGY BALANCE; ENERGY EXPENDITURE; FOOD INTAKE; GLUCONEOGENESIS; GLUCOSE HOMEOSTASIS; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTESTINE FLORA; LIPID ABSORPTION; LIPID STORAGE; LIPOGENESIS; LIPOLYSIS; LIVER FUNCTION; NONHUMAN; OBESITY; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SKELETAL MUSCLE; STOMACH ABSORPTION; STOMACH ACID SECRETION; STOMACH EMPTYING; WEIGHT CONTROL; BODY WEIGHT; DRUG EFFECTS; GASTROINTESTINAL TRACT; METABOLISM; MICROBIOLOGY; MICROFLORA; PHYSIOLOGY;

ADIPOSE TISSUE; BODY WEIGHT; ENERGY INTAKE; FATTY ACIDS, VOLATILE; GASTROINTESTINAL TRACT; HUMANS; INSULIN RESISTANCE; MICROBIOTA;

EID: 84941879755     PISSN: 17595029     EISSN: 17595037     Source Type: Journal    
DOI: 10.1038/nrendo.2015.128     Document Type: Review

References (180)

1. Shulman G. I. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N. Engl. J. Med. 371, 1131-1141 (2014
2. Grundy S. M. Obesity, metabolic syndrome, and cardiovascular disease. J. Clin. Endocrinol. Metab. 89, 2595-2600 (2004
3. Kahn S. E., Hull R. L., & Utzschneider K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840-846 (2006
4. Bäckhed F., et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718-15723 (2004
5. Turnbaugh P. J., et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027-1031 (2006
6. Membrez M., et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 22, 2416-2426 (2008
7. Andersson U., et al. Probiotics lower plasma glucose in the high-fat fed C57BL/6J mouse. Benef. Microbes 1, 189-196 (2010
8. Vrieze A., et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol. 60, 824-831 (2014
9. Vrieze A., et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913-916 (2012
10. Topping D. L., & Clifton P. M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81, 1031-1064 (2001
11. De Vadder F., et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84-96 (2014
12. Gao Z., et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509-1517 (2009
13. Lin H. V., et al. Butyrate and propionate protect. against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3 independent mechanisms. PLoS ONE 7, e35240 (2012
14. Frost G., et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 5, 3611 (2014
15. Freeland K. R., & Wolever T. Acute effects of intravenous and rectal acetate on glucagon-like peptide 1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br. J. Nutr. 103, 460-466 (2010
16. den Besten G., et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes 64, 2398-2408 (2015
17. Murphy E., et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 1635-1642 (2010
18. Al-Lahham S. H., et al. Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur. J. Clin. Invest. 42, 357-364 (2012
19. Al-Lahham S. H., et al. Regulation of adipokine production in human adipose tissue by propionic acid. Eur. J. Clin. Invest. 40, 401-407 (2010
20. Macfarlane G. T., & Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J. AOAC Int. 95, 50-60 (2012
21. Cummings J., Pomare E., Branch W., Naylor C., & Macfarlane G. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221 (1987
22. Blachier F., Mariotti F., Huneau J., & Tome D. Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33, 547-562 (2007
23. Geypens B., et al. Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. Gut 41, 70-76 (1997
24. Macfarlane G., Gibson G., Beatty E., & Cummings J. Estimation of short-chain fatty acid production from protein by human intestinal bacteria based on branched-chain fatty acid measurements. FEMS Microbiol. Lett. 101, 81-88 (1992
25. Corpet D. E., et al. Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein. Nutr. Cancer 23, 271-281 (1995
26. Windey K., De Preter V., & Verbeke K. Relevance of protein fermentation to gut health. Mol. Nutr. Food Res. 56, 184-196 (2012
27. Wong J. M., de Souza R., Kendall C. W., Emam A., & Jenkins D. J. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 40, 235-243 (2006
28. Schwiertz A., et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18, 190-195 (2009
29. Fernandes J., Su W., Rahat-Rozenbloom S., Wolever T., & Comelli E. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr. Diabetes 4, e121 (2014
30. Cummings J. H., & Macfarlane G. T. Colonic microflora: nutrition and health. Nutrition 13, 476-478 (1997
31. McBurney M. I., & Thompson L. U. In vitro fermentabilities of purified fiber supplements. J. Food Sci. 54, 347-350 (1989
32. McBurney M., Thompson L., Cuff D., & Jenkins D. Comparison of ileal effluents, dietary fibers, and whole foods in predicting the physiological importance of colonic fermentation. Am. J. Gastroenterol. 83, 536-540 (1988
33. Venema K. Microbial metabolites produced by the colonic microbiota as drivers for immunomodulation in the host. FASEB J. 27, 643.12 (2013
34. Pylkas A., Juneja L., & Slavin J. Comparison of different fibers for in vitro production of short chain fatty acids by intestinal microflora. J. Med. Food 8, 113-116 (2005
35. Lampe J., Fredstrom S., Slavin J., & Potter J. Sex differences in colonic function: a randomised trial. Gut 34, 531-536 (1993
36. Lampe J., Wetsch R., Thompson W., & Slavin J. Gastrointestinal effects of sugarbeet fiber and wheat bran in healthy men. Eur. J. Clin. Nutr. 47, 543-548 (1993
37. Owens F., & Isaacson H. Ruminal microbial yields: factors influencing synthesis and bypass. Fed. Proc. 36, 198-202 (1977
38. Lewis S., & Heaton K. Increasing butyrate concentration in the distal colon by accelerating intestinal transit. Gut 41, 245-251 (1997
39. El Oufir L., et al. Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria. Eur. J. Clin. Nutr. 54, 603-609 (2000
40. Ruppin H., Bar-Meir S., Soergel K., Wood C., & Schmitt M. Jr. Absorption of short-chain fatty acids by the colon. Gastroenterology 78, 1500-1507 (1980
41. Titus E., & Ahearn G. A. Short-chain fatty acid transport in the intestine of a herbivorous teleost. J. Exp. Biol. 135, 77-94 (1988
42. Ritzhaupt A., Wood I. S., Ellis A., Hosie K. B., & Shirazi-Beechey S. P. Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L lactate as well as butyrate. J. Physiol. 513, 719-732 (1998
43. Moschen I., Bröer A., Galic S., Lang F.& Bröer S. Significance of short chain fatty acid transport by members of the monocarboxylate transporter family (MCT). Neurochem. Res. 37, 2562-2568 (2012
44. Bloemen J. G., et al. Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin. Nutr. 28, 657-661 (2009
45. Araghizadeh A., & Abdelnaby A. in Colorectal Surgery (eds Bailey H. R., Billingham R. P., Stamos M. J., & Snyder M. J.) 3-17 (Elsevier Health Sciences, 2012
46. Bloemen J. G., et al. Short chain fatty acids exchange: Is the cirrhotic, dysfunctional liver still able to clear them?. Clin. Nutr. 29, 365-369 (2010
47. Robertson M. D., Bickerton A. S., Dennis A. L., Vidal H., & Frayn K. N. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am. J. Clin. Nutr. 82, 559-567 (2005
48. Roediger W. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21, 793-798 (1980
49. Roediger W. E. W. in Physiological and Clinical Aspects of Short-Chain Fatty Acids (eds Cummings J. H., Rombeau J. L., & Sakata T.) 337-351 (Cambridge University Press, 1995
50. Ardawi M., & Newsholme E. Fuel utilization in colonocytes of the rat. Biochem. J. 231, 713-719 (1985
51. Frankel W., et al. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology 106, 375-380 (1994
52. Brown A. J., et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278, 11312-11319 (2003
53. Le Poul E., et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481-25489 (2003
54. Karaki S., et al. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J. Mol. Histol. 39, 135-142 (2008
55. Tazoe H., et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed. Res. 30, 149-156 (2009
56. Thangaraju M., et al. GPR109A is a G protein coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 69, 2826-2832 (2009
57. Liu F., et al. The expression of GPR109A, NF κB and IL 1β in peripheral blood leukocytes from patients with type 2 diabetes. Ann. Clin. Lab. Sci. 44, 443-448 (2014
58. Taggart A. K., et al. (D) β-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA G. J. Biol. Chem. 280, 26649-26652 (2005
59. Tunaru S., et al. PUMA G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat. Med. 9, 352-355 (2003
60. Pluznick J. L., 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 110, 4410-4415 (2013
61. Hellman B., Larsson S., & Westman S. Acetate metabolism in isolated epididymal adipose tissue from obese-hyperglycemic mice of different ages. Acta Physiol. Scand. 56, 189-198 (1962
62. Villee C. The effect of insulin on the incorporation of C14-labeled pyruvate and acetate into lipid and protein. Anat. Rec. 101, 680 (1948
63. Feller D. Metabolism of adipose tissue. I. Incorporation of acetate carbon into lipides by slices of adipose tissue. J. Biol. Chem. 206, 171-180 (1954
64. Elwood J., Marcó A., & Van Bruggen J. Lipid metabolism in the diabetic rat. IV. Metabolism of acetate, acetoacetate, butyrate, and mevalonate in vitro. J. Biol. Chem. 235, 573-577 (1960
65. Wong R. K., & Van Bruggen J. Lipid metabolism in the diabetic rat. I. Acetate metabolism and lipid synthesis in vivo. J. Biol. Chem. 235, 26-29 (1960
66. Reshef L., Niv J., & Shapiro B. Effect of propionate on lipogenesis in adipose tissue. J. Lipid Res. 8, 682-687 (1967
67. Sakata T. Effects of indigestible dietary bulk and short chain fatty acids on the tissue weight and epithelial cell proliferation rate of the digestive tract in rats. J. Nutr. Sci. Vitaminol. (Tokyo) 32, 355-362 (1986
68. Boillot J., et al. Effects of dietary propionate on hepatic glucose production, whole-body glucose utilization, carbohydrate and lipid metabolism in normal rats. Br. J. Nutr. 73, 241-251 (1995
69. Crouse J. R., Gerson C. D., DeCarli L. M., & Lieber C. S. Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man. J. Lipid Res. 9, 509-512 (1968
70. Björntorp P., & Hood B. Studies on adipose tissue from obese patients with or without diabetes mellitus. Acta Med. Scand. 179, 221-227 (1966
71. Todesco T., Rao A. V., Bosello O., & Jenkins D. Propionate lowers blood glucose and alters lipid metabolism in healthy subjects. Am. J. Clin. Nutr. 54, 860-865 (1991
72. Wolever T., Brighenti F., Royall D., Jenkins A., & Jenkins D. Effect of rectal infusion of short chain fatty acids in human subjects. Am. J. Gastroenterol. 84, 1027-1033 (1989
73. Zoetendal E. G., Collier C. T., Koike S., Mackie R. I., & Gaskins H. R. Molecular ecological analysis of the gastrointestinal microbiota: a review. J. Nutr. 134, 465-472 (2004
74. Muyzer G., De Waal E. C., & Uitterlinden A. G. Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl. Environ. Microbiol. 59, 695-700 (1993
75. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat. Rev. Microbiol. 11, 639-647 (2013
76. Hartstra A. V., Bouter K. E., Bäckhed F., & Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 38, 159-165 (2015
77. Turnbaugh P. J., et al. A core gut microbiome in obese and lean twins. Nature 457, 480-484 (2008
78. Pedersen M. H., Lauritzen L., & Hellgren L. I. Fish oil combined with SCFA synergistically prevent tissue accumulation of NEFA during weight loss in obese mice. Br. J. Nutr. 106, 1449-1456 (2011
79. Ridaura V. K., et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013
80. Fujii H., et al. Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. Nutr. J. 12, 159 (2013
81. Konings E., Schoffelen P. F., Stegen J., & Blaak E. E. Effect of polydextrose and soluble maize fibre on energy metabolism, metabolic profile and appetite control in overweight men and women. Br. J. Nutr. 111, 111-121 (2014
82. Reichert R. G., et al. Decreasing cardiovascular risk factors in obese individuals using a combination of PGX® meal replacements and PGX® granules in a 12-week clinical weight modification program. J. Complement. Integr. Med. 10, 135-142 (2013
83. Hashizume C., et al. Improvement effect of resistant maltodextrin in humans with metabolic syndrome by continuous administration. J. Nutr. Sci. Vitaminol. 58, 423-430 (2012
84. Cani P. D., et al. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am. J. Clin. Nutr. 90, 1236-1243 (2009
85. Cani P. D., Joly E., Horsmans Y., & Delzenne N. M. Oligofructose promotes satiety in healthy human: a pilot study. Eur. J. Clin. Nutr. 60, 567-572 (2006
86. Vulevic J., Juric A., Tzortzis G., & Gibson G. R. A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults. J. Nutr. 143, 324-331 (2013
87. Daud N. M., et al. The impact of oligofructose on stimulation of gut hormones, appetite regulation and adiposity. Obesity 22, 1430-1438 (2014
88. Dewulf E., et al. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 62, 1112-1121 (2013
89. Parnell J. A., & Reimer R. A. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am. J. Clin. Nutr. 89, 1751-1759 (2009
90. Royall D., Wolever T., & Jeejeebhoy K. N. Clinical significance of colonic fermentation. Am. J. Gastroenterol. 85, 1307-1312 (1990
91. Alhabeeb H., Chambers E., Frost G., Morrison D., & Preston T. Inulin propionate ester increases satiety and decreases appetite but does not affect gastric emptying in healthy humans. Proc. Nutr. Soc. 73, E21 (2014
92. Chambers E. S., et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut http://dx.doi.org/10.1136/gutjnl-2014-307913
93. Kondo T., Kishi M., Fushimi T., Ugajin S., & Kaga T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci. Biotechnol. Biochem. 73, 1837-1843 (2009
94. Theodorakis M. J., et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP 1 and GIP. Am. J. Physiol. Endocrinol. Metab. 290, E550-E559 (2006
95. Roberge J. N., & Brubaker P. L. Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 133, 233-240 (1993
96. De Silva A., & Bloom S. R. Gut hormones and appetite control: a focus on PYY and GLP 1 as therapeutic targets in obesity. Gut Liver 6, 10-20 (2012
97. Savage A., Adrian T., Carolan G., Chatterjee V., & Bloom S. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut 28, 166-170 (1987
98. Murphy K. G., & Bloom S. R. Gut hormones and the regulation of energy homeostasis. Nature 444, 854-859 (2006
99. Näslund E., et al. GLP 1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am. J. Physiol. 277, R910-R916 (1999
100. Schjoldager B., Mortensen P., Christiansen J., Orskov C., & Holst J. GLP 1 (glucagon-like peptide 1) and truncated GLP 1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig. Dis. Sci. 34, 703-708 (1989
101. Tolhurst G., et al. Short-chain fatty acids stimulate glucagon-like peptide 1 secretion via the G protein coupled receptor FFAR2. Diabetes 61, 364-371 (2012
102. Psichas A., 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. 39, 424-429 (2014
103. Reimer R. A., et al. A human cellular model for studying the regulation of glucagon-like peptide 1 secretion. Endocrinology 142, 4522-4528 (2001
104. Psichas A., et al. Short chain fatty acids stimulate the release of gut hormone peptide YY from human primary enteroendocrine L cells. Proc. Physiol. Soc. 27, PC331 (2012
105. Karaki S., et al. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res. 324, 353-360 (2006
106. Cani P. D., Dewever C., & Delzenne N. M. Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide 1 and ghrelin) in rats. Br. J. Nutr. 92, 521-526 (2004
107. Zhou J., et al. Dietary resistant starch upregulates total GLP 1 and PYY in a sustained day-long manner through fermentation in rodents. Am. J. Physiol. Endocrinol. Metab. 295, E1160-E1166 (2008
108. Cani P. D., Neyrinck A. M., Maton N., & Delzenne N. M. Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1. Obesity Res. 13, 1000-1007 (2005
109. Zhou J., et al. Peptide YY and proglucagon mRNA expression patterns and regulation in the gut. Obesity 14, 683-689 (2006
110. Cani P. D., Hoste S., Guiot Y., & Delzenne N. M. Dietary non-digestible carbohydrates promote L cell differentiation in the proximal colon of rats. Br. J. Nutr. 98, 32-37 (2007
111. Pedersen C., et al. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study. Appetite 66, 44-53 (2013
112. Wichmann A., et al. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe 14, 582-590 (2013
113. Jiang L., et al. Increased brain uptake and oxidation of acetate in heavy drinkers. J. Clin. Invest. 123, 1605-1614 (2013
114. Xiong Y., et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc. Natl Acad. Sci. USA 101, 1045-1050 (2004
115. Soliman M., et al. Inverse regulation of leptin mRNA expression by short-and long-chain fatty acids in cultured bovine adipocytes. Domest. Anim. Endocrinol. 33, 400-409 (2007
116. Lee S., & Hossner K. Coordinate regulation of ovine adipose tissue gene expression by propionate. J. Anim. Sci. 80, 2840-2849 (2002
117. Ioffe E., Moon B., Connolly E., & Friedman J. M. Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proc. Natl Acad. Sci. USA 95, 11852-11857 (1998
118. Maffei M., et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1, 1155-1161 (1995
119. Frederich R. C., et al. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1, 1311-1314 (1995
120. 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. 57, 5982-5986 (2009
121. Kimura I., 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 108, 8030-8035 (2011
122. Mithieux G., & Gautier-Stein A. Intestinal glucose metabolism revisited. Diabetes Res. Clin. Pract. 105, 295-301 (2014
123. Ge H., et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 149, 4519-4526 (2008
124. Aberdein N., Schweizer M., & Ball D. Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3 L1 mature adipocytes. Adipocyte 3, 121-125 (2014
125. Rumberger J. M, Arch J. R., & Green A. Butyrate and other short-chain fatty acids increase the rate of lipolysis in 3T3 L1 adipocytes. PeerJ 2, e611 (2013
126. Hong Y. H., et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 5092-5099 (2005
127. Kimura I., et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829 (2013
128. Inoue D., Tsujimoto G., & Kimura I. Regulation of energy homeostasis by GPR41. Front. Endocrinol. (Laussane) 5, 81 (2014
129. Zaibi M. S., et al. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett. 584, 2381-2386 (2010
130. Frost G., 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 4, e128 (2014
131. Merkel M., Eckel R. H., & Goldberg I. J. Lipoprotein lipase genetics, lipid uptake, and regulation. J. Lipid Res. 43, 1997-2006 (2002
132. Grootaert C., et al. Bacterial monocultures, propionate, butyrate and H2O2 modulate the expression, secretion and structure of the fasting induced adipose factor in gut epithelial cell lines. Environ. Microbiol. 13, 1778-1789 (2011
133. Haberland M., Carrer M., Mokalled M. H., Montgomery R. L., & Olson E. N. Redundant control of adipogenesis by histone deacetylases 1 and 2. J. Biol. Chem. 285, 14663-14670 (2010
134. Li G., Yao W., & Jiang H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. J. Nutr. 144, 1887-1895 (2014
135. Dewulf E. M., et al. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J. Nutr. Biochem. 22, 712-722 (2011
136. Dewulf E. M., et al. Evaluation of the relationship between GPR43 and adiposity in human. Nutr. Metab. 10, 11 (2013
137. Goossens G. H. The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206-218 (2008
138. Tilg H., & Moschen A. R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 6, 772-783 (2006
139. Apovian C. M., et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler. Thromb. Vasc. Biol. 28, 1654-1659 (2008
140. Chaudhry A., & Rudensky A. Y. Control of inflammation by integration of environmental cues by regulatory T cells. J. Clin. Invest. 123, 939-944 (2013
141. Nishimura S., et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15, 914-920 (2009
142. Mazurek T., et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108, 2460-2466 (2003
143. Smith P. M., et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569-573 (2013
144. Furusawa Y., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446-450 (2013
145. Arpaia N., et al. Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation. Nature 504, 451-455 (2013
146. Mariadason J. M., Barkla D. H., & Gibson P. R. Effect of short-chain fatty acids on paracellular permeability in Caco 2 intestinal epithelium model. Am. J. Physiol. 272, G705-G712 (1997
147. Malago J., et al. Differential modulation of enterocyte-like Caco 2 cells after exposure to short-chain fatty acids. Food Addit. Contam. 20, 427-437 (2003
148. Suzuki T., Yoshida S., & Hara H. Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability. Br. J. Nutr. 100, 297-305 (2008
149. Elamin E. E., Masclee A. A., Dekker J., Pieters H. J., & Jonkers D. M. Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco 2 cell monolayers. J. Nutr. 143, 1872-1881 (2013
150. Macia L., et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734 (2015
151. Cani P. D., et al. Selective increases of bifidobacteria in gut microflora improve high fat diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50, 2374-2383 (2007
152. Cani P. D., et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761-1772 (2007
153. Mehta N. N., et al. Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes 59, 172-181 (2010
154. Vila I. K., et al. Immune cell toll-like receptor 4 mediates the development of obesity-and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 7, 1116-1129 (2014
155. Muccioli G. G., et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 6, 392 (2010
156. 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. 13, 2826-2832 (2007
157. Liu T., et al. Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF κB pathway in RAW264.7 cells. Inflammation 35, 1676-1684 (2012
158. Cox M. A., et al. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E2 and cytokines. World J. Gastroenterol. 15, 5549-5557 (2009
159. Ohira H., et al. Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages. J. Atheroscler. Thromb. 20, 425-442 (2013
160. Koves T. R., et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7, 45-56 (2008
161. Corpeleijn E., Saris W., & Blaak E. Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle. Obes. Rev. 10, 178-193 (2009
162. Yamashita H., 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. 73, 570-576 (2009
163. Fushimi T., et al. Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats. J. Nutr. 131, 1973-1977 (2001
164. Bonini J. A., Anderson S. M., & Steiner D. F. Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem. Biophys. Res. Comm. 234, 190-193 (1997
165. Chai W., et al. Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes 61, 888-896 (2012
166. Cherbut C., et al. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am. J. Physiol. 275, G1415-G1422 (1998
167. Tazoe H., et al. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J. Physiol. Pharmacol. 59, 251-262 (2008
168. Samuel B. S., 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 105, 16767-16772 (2008
169. den Besten G., et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am. J. Physiol. 305, G900-G910 (2013
170. Demigne C., et al. Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. Br. J. Nutr. 74, 209-219 (1995
171. Hardie D., & Pan D. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans. 30, 1064-1070 (2002
172. Zhang B. B., Zhou G., & Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 9, 407-416 (2009
173. Li X., et al. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes. PLoS ONE 8, e67880 (2013
174. Yamashita H., et al. Improvement of obesity and glucose tolerance by acetate in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci. Biotechnol. Biochem. 71, 1236-1243 (2007
175. Sakakibara S., Yamauchi T., Oshima Y., Tsukamoto Y., & Kadowaki T. Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK A(y) mice. Biochem. Biophys. Res. Comm. 344, 597-604 (2006
176. Endo H., Niioka M., Kobayashi N., Tanaka M., & Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis. PLoS ONE 8, e63388 (2013
177. Wolever T., Spadafora P., & Eshuis H. Interaction between colonic acetate and propionate in humans. Am. J. Clin. Nutr. 53, 681-687 (1991
178. Laurent C., et al. Effect of acetate and propionate on fasting hepatic glucose production in humans. Eur. J. Clin. Nutr. 49, 484-491 (1995
179. Fernandes J., Vogt J., & Wolever T. M. Intravenous acetate elicits a greater free fatty acid rebound in normal than hyperinsulinaemic humans. Eur. J. Clin. Nutr. 66, 1029-1034 (2012
180. Venter C. S., Vorster H. H., & Cummings J. H. Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers. Am. J. Gastroenterol. 85, 549-553 (1990