The metabolic fate of acetate in cancer

Nature Reviews Cancer

Volumn 16, Issue 11, 2016, Pages 708-717

  Schug, Zachary T ^a,b   Vande Voorde, Johan ^a   Gottlieb, Eyal ^a  

^a BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^b WISTAR INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETATE COENZYME A LIGASE; ACETIC ACID; ACETIC ACID C 11; ACETYL COENZYME A; FATTY ACID; FLUORODEOXYGLUCOSE F 18; HISTONE; SIRTUIN; TRICARBOXYLIC ACID; ACETIC ACID DERIVATIVE;

APOPTOSIS; BIOENERGY; CANCER CELL; CANCER PATIENT; CELL FATE; CELL HYPOXIA; CELL MEMBRANE; CELL STRESS; CELL TRANSPORT; CITRIC ACID CYCLE; ENERGY YIELD; ERYTHROPOIESIS; FATTY ACID OXIDATION; FATTY ACID SYNTHESIS; HISTONE ACETYLATION; HUMAN; LIPOGENESIS; METABOLISM; NEOPLASM; NONHUMAN; NUTRIENT AVAILABILITY; NUTRITION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; TUMOR XENOGRAFT; INTESTINE FLORA; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ACETATES; ACETYL COENZYME A; GASTROINTESTINAL MICROBIOME; HUMANS; METABOLIC NETWORKS AND PATHWAYS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84983437346     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc.2016.87     Document Type: Review

References (120)

1. Medes, G., Friedmann, B., & Weinhouse, S. Fatty acid metabolism. VIII. Acetate metabolism in vitro during hepatocarcinogenesis by p dimethylaminoazobenzene. Cancer Res. 16, 57-62 (1956
2. Medes, G., & Weinhouse, S. Metabolism of neoplastic tissue. XIII. Substrate competition in fatty acid oxidation in ascites tumor cells. Cancer Res. 18, 352-359 (1958
3. Medes, G., Paden, G., & Weinhouse, S. Metabolism of neoplastic tissues. XI. Absorption and oxidation of dietary fatty acids by implanted tumors. Cancer Res. 17, 127-133 (1957
4. Thomlinson, R. H., & Gray, L. H. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br. J. Cancer 9, 539-549 (1955
5. Nath, A., & Chan, C. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers. Sci. Rep. 6, 18669 (2016
6. Zaugg, K., et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev. 25, 1041-1051 (2011
7. Gajewski, T. F., Schreiber, H., & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 14, 1014-1022 (2013
8. Azzi, S., Hebda, J. K., & Gavard, J. Vascular permeability and drug delivery in cancers. Front. Oncol. 3, 211 (2013
9. Joint FAO/WHO Codex Alimentarius Commission. Codex general standard for food additives http://www. fao.org/fao-who-codexalimentarius/download/standards/4/CXS-192-2015e.pdf (Joint FAO/WHO Codex Alimentarius Commission, 2015
10. Suematsu, N., & Isohashi, F. Molecular cloning and functional expression of human cytosolic acetyl-CoA hydrolase. Acta Biochim. Pol. 53, 553-561 (2006
11. Horibata, Y., Ando, H., Itoh, M., & Sugimoto, H. Enzymatic and transcriptional regulation of the cytoplasmic acetyl-CoA hydrolase ACOT12. J. Lipid Res. 54, 2049-2059 (2013
12. Scheppach, W., Pomare, E. W., Elia, M., & Cummings, J. H. The contribution of the large intestine to blood acetate in man. Clin. Sci. (Lond.) 80, 177-182 (1991
13. Louis, P., Hold, G. L., & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 12, 661-672 (2014
14. Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P., & Macfarlane, G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221-1227 (1987
15. Schuchmann, K., & Muller, V. Autotrophy at the thermodynamic limit of life: a model for energy conservation in acetogenic bacteria. Nat. Rev. Microbiol. 12, 809-821 (2014
16. Rey, F. E., et al. Dissecting the in vivo metabolic potential of two human gut acetogens. J. Biol. Chem. 285, 22082-22090 (2010
17. Donohoe, D. R., et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13, 517-526 (2011
18. 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
19. Rocco, A., Compare, D., Angrisani, D., Sanduzzi Zamparelli, M., & Nardone, G. Alcoholic disease: liver and beyond. World J. Gastroenterol. 20, 14652-14659 (2014
20. Nuutinen, H., Lindros, K., Hekali, P., & Salaspuro, M. Elevated blood acetate as indicator of fast ethanol elimination in chronic alcoholics. Alcohol 2, 623-626 (1985
21. Lundquist, F., Tygstrup, N., Winkler, K., Mellemgaard, K., & Munck-Petersen, S. Ethanol metabolism and production of free acetate in the human liver. J. Clin. Invest. 41, 955-961 (1962
22. Seitz, H. K., & Stickel, F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat. Rev. Cancer 7, 599-612 (2007
23. Kendrick, S. F., et al. Acetate, the key modulator of inflammatory responses in acute alcoholic hepatitis. Hepatology 51, 1988-1997 (2010
24. Schug, Z. T., et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27, 57-71 (2015
25. Comerford, S. A., et al. Acetate dependence of tumors. Cell 159, 1591-1602 (2014
26. Fleming, S. E., Choi, S. Y., & Fitch, M. D. Absorption of short-chain fatty acids from the rat cecum in vivo. J. Nutr. 121, 1787-1797 (1991
27. Reynolds, D. A., Rajendran, V. M., & Binder, H. J. Bicarbonate-stimulated [14C]butyrate uptake in basolateral membrane vesicles of rat distal colon. Gastroenterology 105, 725-732 (1993
28. Chu, S., & Montrose, M. H. Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids. Proc. Natl Acad. Sci. USA 92, 3303-3307 (1995
29. Miyauchi, S., Gopal, E., Fei, Y. J., & Ganapathy, V. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na+-coupled transporter for short-chain fatty acids. J. Biol. Chem. 279, 13293-13296 (2004
30. Coady, M. J., et al. The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. J. Physiol. 557, 719-731 (2004
31. Li, H., et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc. Natl Acad. Sci. USA 100, 8412-8417 (2003
32. Lin, H. Y., et al. Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness. Urology 78, 971.e1-971.e9 (2011
33. Ullah, M. S., Davies, A. J., & Halestrap, A. P. The plasma membrane lactate transporter MCT4, but not MCT1, is up regulated by hypoxia through a HIF 1α dependent mechanism. J. Biol. Chem. 281, 9030-9037 (2006
34. Parks, S. K., Chiche, J., & Pouyssegur, J. Disrupting proton dynamics and energy metabolism for cancer therapy. Nat. Rev. Cancer 13, 611-623 (2013
35. Kirat, D., & Kato, S. Monocarboxylate transporter 1 (MCT1) mediates transport of short-chain fatty acids in bovine caecum. Exp. Physiol. 91, 835-844 (2006
36. Pinheiro, C., et al. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch. 452, 139-146 (2008
37. Moschen, I., Broer, A., Galic, S., Lang, F., & Broer, S. Significance of short chain fatty acid transport by members of the monocarboxylate transporter family (MCT). Neurochem. Res. 37, 2562-2568 (2012
38. Jackson, V. N., & Halestrap, A. P. The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2′,7′ bis(carboxyethyl)-5(6)-carboxyfluorescein. J. Biol. Chem. 271, 861-868 (1996
39. Olivares, O., Dabritz, J. H., King, A., Gottlieb, E., & Halsey, C. Research into cancer metabolomics: towards a clinical metamorphosis. Semin. Cell Dev. Biol. 43, 52-64 (2015
40. Bola, B. M., et al. Inhibition of monocarboxylate transporter 1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol. Cancer Ther. 13, 2805-2816 (2014
41. Fujino, T., Kondo, J., Ishikawa, M., Morikawa, K., & Yamamoto, T. T. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J. Biol. Chem. 276, 11420-11426 (2001
42. Luong, A., Hannah, V. C., Brown, M. S., & Goldstein, J. L. Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins. J. Biol. Chem. 275, 26458-26466 (2000
43. Watkins, P. A., Maiguel, D., Jia, Z., & Pevsner, J. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J. Lipid Res. 48, 2736-2750 (2007
44. Tucek, S. Subcellular distribution of acetyl-CoA synthetase, ATP citrate lyase, citrate synthase, choline acetyltransferase, fumarate hydratase and lactate dehydrogenase in mammalian brain tissue. J. Neurochem. 14, 531-545 (1967
45. Hatzivassiliou, G., et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8, 311-321 (2005
46. Zaidi, N., Royaux, I., Swinnen, J. V., & Smans, K. ATP citrate lyase knockdown induces growth arrest and apoptosis through different cell-and environment-dependent mechanisms. Mol. Cancer Ther. 11, 1925-1935 (2012
47. Wellen, K. E., et al. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076-1080 (2009
48. Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., & Thompson, C. B. ATP citrate lyase is an important component of cell growth and transformation. Oncogene 24, 6314-6322 (2005
49. Kim, J. W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. HIF 1 mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3, 177-185 (2006
50. Spriet, L. L., et al. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting. J. Appl. Physiol. 96, 2082-2087 (2004
51. Kamphorst, J. J., Chung, M. K., Fan, J., & Rabinowitz, J. D. Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate. Cancer Metab. 2, 23 (2014
52. Mashimo, T., et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159, 1603-1614 (2014
53. Kuhajda, F. P., et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc. Natl Acad. Sci. USA 91, 6379-6383 (1994
54. Xu, M., et al. An acetate switch regulates stress erythropoiesis. Nat. Med. 20, 1018-1026 (2014
55. Maher, E. A., et al. Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed. 25, 1234-1244 (2012
56. Bjornson, E., et al. Stratification of hepatocellular carcinoma patients based on acetate utilization. Cell Rep. 13, 2014-2026 (2015
57. Schug, Z. T., Vande Voorde, J., & Gottlieb, E. The nurture of tumors can drive their metabolic phenotype. Cell Metab. 23, 391-392 (2016
58. Davidson, S. M., et al. Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer. Cell Metab. 23, 517-528 (2016
59. McBrian, M. A., et al. Histone acetylation regulates intracellular pH. Mol. Cell 49, 310-321 (2013
60. Takahashi, H., McCaffery, J. M., Irizarry, R. A., & Boeke, J. D. Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Mol. Cell 23, 207-217 (2006
61. Gao, X., et al. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat. Commun. 7, 11960 (2016
62. Chen, R., et al. The acetate/ACSS2 switch regulates HIF 2 stress signaling in the tumor cell microenvironment. PLoS ONE 10, e0116515 (2015
63. Fan, J., Krautkramer, K. A., Feldman, J. L., & Denu, J. M. Metabolic regulation of histone post-translational modifications. ACS Chem. Biol. 10, 95-108 (2015
64. Lee, J. V., et al. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab. 20, 306-319 (2014
65. Rajendran, P., Williams, D. E., Ho, E., & Dashwood, R. H. Metabolism as a key to histone deacetylase inhibition. Crit. Rev. Biochem. Mol. Biol. 46, 181-199 (2011
66. Martinez-Pastor, B., Cosentino, C., & Mostoslavsky, R. A tale of metabolites: the cross-talk between chromatin and energy metabolism. Cancer Discov. 3, 497-501 (2013
67. Yoshii, Y., et al. Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism. Cancer Sci. 100, 821-827 (2009
68. Sonveaux, P., et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest. 118, 3930-3942 (2008
69. Houtkooper, R. H., Pirinen, E., & Auwerx, J. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 13, 225-238 (2012
70. Chen, R., Dioum, E. M., Hogg, R. T., Gerard, R. D., & Garcia, J. A. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner. J. Biol. Chem. 286, 13869-13878 (2011
71. Starai, V. J., Celic, I., Cole, R. N., Boeke, J. D., & Escalante-Semerena, J. C. Sir2 dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science 298, 2390-2392 (2002
72. Schwer, B., Bunkenborg, J., Verdin, R. O., Andersen, J. S., & Verdin, E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc. Natl Acad. Sci. USA 103, 10224-10229 (2006
73. Hallows, W. C., Lee, S., & Denu, J. M. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl Acad. Sci. USA 103, 10230-10235 (2006
74. 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
75. Priyadarshini, M., et al. An acetate-specific GPCR, FFAR2, regulates insulin secretion. Mol. Endocrinol. 29, 1055-1066 (2015
76. Tang, C., et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21, 173-177 (2015
77. 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
78. Hong, Y. H., et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 5092-5099 (2005
79. Peck, B., et al. Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer Metab. 4, 6 (2016
80. Smith, P. M., et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569-573 (2013
81. Erny, D., et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18, 965-977 (2015
82. Correa-Oliveira, R., Fachi, J. L., Vieira, A., Sato, F. T., & Vinolo, M. A. Regulation of immune cell function by short-chain fatty acids. Clin. Transl Immunol. 5, e73 (2016
83. Hatanaka, H., et al. Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening. Cancer Sci. 101, 54-59 (2010
84. Tang, Y., Chen, Y., Jiang, H., Robbins, G. T., & Nie, D. G Protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int. J. Cancer 128, 847-856 (2011
85. Yonezawa, T., Kobayashi, Y., & Obara, Y. Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF 7 human breast cancer cell line. Cell. Signal. 19, 185-193 (2007
86. Shou, Y., Lu, J., Chen, T., Ma, D., & Tong, L. Correlation of fluorodeoxyglucose uptake and tumor-proliferating antigen Ki 67 in lymphomas. J. Cancer Res. Ther. 8, 96-102 (2012
87. Riedl, C. C., et al. 18F FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases. J. Nucl. Med. 48, 771-775 (2007
88. Gillies, R. J., Schornack, P. A., Secomb, T. W., & Raghunand, N. Causes and effects of heterogeneous perfusion in tumors. Neoplasia 1, 197-207 (1999
89. Yamamoto, Y., et al. 11C acetate PET in the evaluation of brain glioma: comparison with 11C methionine and 18F FDG-PET. Mol. Imaging Biol. 10, 281-287 (2008
90. Wong, T. Z., van Der Westhuizen, G. J., & Coleman, R. E. Positron emission tomography imaging of brain tumors. Neuroimaging Clin. N. Am. 12, 615-626 (2002
91. Yoshii, Y., Furukawa, T., Saga, T., & Fujibayashi, Y. Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: overview and application. Cancer Lett. 356, 211-216 (2015
92. Vavere, A. L., Kridel, S. J., Wheeler, F. B., & Lewis, J. S. 1 11C acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer. J. Nucl. Med. 49, 327-334 (2008
93. Oyama, N., et al. 11C acetate PET imaging of prostate cancer. J. Nucl. Med. 43, 181-186 (2002
94. Ponde, D. E., et al. 18F fluoroacetate: a potential acetate analog for prostate tumor imaging-in vivo evaluation of 18F fluoroacetate versus 11C acetate. J. Nucl. Med. 48, 420-428 (2007
95. Jadvar, H. Prostate cancer: PET with 18F FDG, 18F-or 11C acetate, and 18F-or 11C choline. J. Nucl. Med. 52, 81-89 (2011
96. Brogsitter, C., Zophel, K., & Kotzerke, J. 18F Choline, 11C choline and 11C acetate PET/CT: comparative analysis for imaging prostate cancer patients. Eur. J. Nucl. Med. Mol. Imaging 40 (Suppl. 1), S18-S27 (2013
97. Schiepers, C., et al. 1 11C acetate kinetics of prostate cancer. J. Nucl. Med. 49, 206-215 (2008
98. Mena, E., et al. 11C Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation. J. Nucl. Med. 53, 538-545 (2012
99. Oyama, N., et al. 11C Acetate PET imaging for renal cell carcinoma. Eur. J. Nucl. Med. Mol. Imaging 36, 422-427 (2009
100. Park, J. W., et al. A prospective evaluation of 18F FDG and 11C acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J. Nucl. Med. 49, 1912-1921 (2008
101. Lewis, D. Y., et al. Late imaging with [1-11C]acetate improves detection of tumor fatty acid synthesis with PET. J. Nucl. Med. 55, 1144-1149 (2014
102. Tsuchida, T., Takeuchi, H., Okazawa, H., Tsujikawa, T., & Fujibayashi, Y. Grading of brain glioma with 1 11C acetate PET: comparison with 18F FDG PET. Nucl. Med. Biol. 35, 171-176 (2008
103. Ho, C. L., et al. 11C acetate PET/CT for metabolic characterization of multiple myeloma: a comparative study with 18F FDG PET/CT. J. Nucl. Med. 55, 749-752 (2014
104. Seltzer, M. A., et al. Radiation dose estimates in humans for 11C acetate whole-body PET. J. Nucl. Med. 45, 1233-1236 (2004
105. Hensley, C. T., et al. Metabolic heterogeneity in human lung tumors. Cell 164, 681-694 (2016
106. Peters, S. G., Pomare, E. W., & Fisher, C. A. Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery. Gut 33, 1249-1252 (1992
107. Dankert, J., Zijlstra, J. B., & Wolthers, B. G. Volatile fatty acids in human peripheral and portal blood: quantitative determination vacuum distillation and gas chromatography. Clin. Chim. Acta 110, 301-307 (1981
108. Gregory, J. F. 3rd, et al. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects. PLoS ONE 8, e63544 (2013
109. Pouteau, E., et al. Production rate of acetate during colonic fermentation of lactulose: a stable-isotope study in humans. Am. J. Clin. Nutr. 68, 1276-1283 (1998
110. Pouteau, E., Meirim, I., Metairon, S., & Fay, L. B. Acetate, propionate and butyrate in plasma: determination of the concentration and isotopic enrichment by gas chromatography/mass spectrometry with positive chemical ionization. J. Mass Spectrom. 36, 798-805 (2001
111. 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
112. Pomare, E. W., Branch, W. J., & Cummings, J. H. Carbohydrate fermentation in the human colon and its relation to acetate concentrations in venous blood. J. Clin. Invest. 75, 1448-1454 (1985
113. Akanji, A. O., Humphreys, S., Thursfield, V., & Hockaday, T. D. The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects. Clin. Chim. Acta 185, 25-34 (1989
114. Akanji, A. O., Ng, L., & Humphreys, S. Plasma acetate levels in response to intravenous fat or glucose/insulin infusions in diabetic and non-diabetic subjects. Clin. Chim. Acta 178, 85-94 (1988
115. 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
116. Fernandes, J., Vogt, J., & Wolever, T. M. Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans. Eur. J. Clin. Nutr. 65, 1279-1286 (2011
117. Simoneau, C., et al. Measurement of whole body acetate turnover in healthy subjects with stable isotopes. Biol. Mass Spectrom. 23, 430-433 (1994
118. Tollinger, C. D., Vreman, H. J., & Weiner, M. W. Measurement of acetate in human blood by gas chromatography: effects of sample preparation, feeding, and various diseases. Clin. Chem. 25, 1787-1790 (1979
119. Pownall, H. J., et al. Effect of moderate alcohol consumption on hypertriglyceridemia: a study in the fasting state. Arch. Intern. Med. 159, 981-987 (1999
120. Muir, J. G., et al. Resistant starch in the diet increases breath hydrogen and serum acetate in human subjects. Am. J. Clin. Nutr. 61, 792-799 (1995