The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance

Cell Reports

Volumn 10, Issue 3, 2015, Pages 326-338

  Warrier, Manya ^a   Shih, Diana M ^f   Burrows, Amy C ^a   Ferguson, Daniel ^a   Gromovsky, Anthony D ^a   Brown, AmandaL ^a   Marshall, Stephanie ^a   McDaniel, Allison ^c   Schugar, Rebecca C ^a   Wang, Zeneng ^a   Sacks, Jessica ^a   Rong, Xin ⁱ   Vallim, ThomasdeAguiar ^f   Chou, Jeff ^c   Ivanova, Pavlina T ^d   Myers, David S ^d   Brown, H Alex ^d   Lee, Richard G ^e   Crooke, Rosanne M ^e   Graham, Mark J ^e   Liu, Xiuli ^a   Parini, Paolo ^g   Tontonoz, Peter ^h,i   Lusis, Aldon J ^f   Hazen, Stanley L ^a   Temel, Ryan E ^b   Brown, J Mark ^a   more..

^a LERNER RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c WAKE FOREST SCHOOL OF MEDICINE   (United States)

^d VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e ISIS PHARMACEUTICALS   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^h HOWARD HUGHES MEDICAL INSTITUTE   (United States)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL ESTER; FLAVIN MONOOXYGENASE 3; FLAVOPROTEIN; LIVER X RECEPTOR; OXYSTEROL; TRIACYLGLYCEROL; TRIMETHYLAMINE OXIDE; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ABCA1 GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; CHOLESTEROL TRANSPORT; DOWN REGULATION; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; ENZYME SYNTHESIS; GENE; GENE TARGETING; HEPATITIS; INTESTINE ABSORPTION; INTESTINE FLORA; LIPID METABOLISM; LPCAT3 GENE; MACROPHAGE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; UPREGULATION;

MUS;

EID: 84921362010     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2014.12.036     Document Type: Article

References (43)

1. Ansaldi M., Théraulaz L., Baraquet C., Panis G., Méjean V. Aerobic TMAO respiration in Escherichia coli. Mol. Microbiol. 2007, 66:484-494.
2. Bennett B.J., de Aguiar Vallim T.Q., Wang Z., Shih D.M., Meng Y., Gregory J., Allayee H., Lee R., Graham M., Crooke R., et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013, 17:49-60.
3. Boden W.E., Probstfield J.L., Anderson T., Chaitman B.R., Desvignes-Nickens P., Koprowicz K., McBride R., Teo K., Weintraub W., Zhao X.Q., et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N.Engl. J. Med. 2011, 365:2255-2267. AIM-HIGH Investigators.
4. Brown M.S., Goldstein J.L. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc. Natl. Acad. Sci. USA 1999, 96:11041-11048.
5. Brown J.M., Hazen S.L. Metaorganismal nutrient metabolism as a basis of cardiovascular disease. Curr. Opin. Lipidol. 2014, 25:48-53.
6. Brown J.M., Bell T.A., Alger H.M., Sawyer J.K., Smith T.L., Kelley K.L., Shah R., Wilson M.D., Davis M.A., Lee R.G., et al. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J.Biol. Chem. 2008, 283:10522-10534.
7. Brufau G., Groen A.K., Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion. Arterioscler. Thromb. Vasc. Biol. 2011, 31:1726-1733.
8. Cashman J.R. Role of flavin-containing monooxygenase in drug development. Expert Opin. Drug Metab. Toxicol. 2008, 4:1507-1521.
9. Cashman J.R., Zhang J. Human flavin-containing monooxygenases. Annu. Rev. Pharmacol. Toxicol. 2006, 46:65-100.
10. Crooke S.T. Advances in understanding the pharmacological properties of antisense oligonucleotides. Adv. Pharmacol. 1997, 40:1-49.
11. Dietschy J.M., Turley S.D. Control of cholesterol turnover in the mouse. J.Biol. Chem. 2002, 277:3801-3804.
12. Glass C.K., Saijo K. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and Tcells. Nat. Rev. Immunol. 2010, 10:365-376.
13. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Borden W.B., Bravata D.M., Dai S., Ford E.S., Fox C.S., et al. Executive summary: heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 2013, 127:143-152. American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
14. Graf G.A., Yu L., Li W.P., Gerard R., Tuma P.L., Cohen J.C., Hobbs H.H. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J.Biol. Chem. 2003, 278:48275-48282.
15. Grefhorst A., Elzinga B.M., Voshol P.J., Plösch T., Kok T., Bloks V.W., van der Sluijs F.H., Havekes L.M., Romijn J.A., Verkade H.J., Kuipers F. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J.Biol. Chem. 2002, 277:34182-34190.
16. Groen A., Kunne C., Jongsma G., van den Oever K., Mok K.S., Petruzzelli M., Vrins C.L., Bull L., Paulusma C.C., Oude Elferink R.P. Abcg5/8 independent biliary cholesterol excretion in Atp8b1-deficient mice. Gastroenterology 2008, 134:2091-2100.
17. Holzer R.G., Park E.J., Li N., Tran H., Chen M., Choi C., Solinas G., Karin M. Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation. Cell 2011, 147:173-184.
18. Jakulj L., Vissers M.N., van Roomen C.P., van der Veen J.N., Vrins C.L., Kunne C., Stellaard F., Kastelein J.J., Groen A.K. Ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice. FEBS Lett. 2010, 584:3625-3628.
19. Joseph S.B., Castrillo A., Laffitte B.A., Mangelsdorf D.J., Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med. 2003, 9:213-219.
20. Khovidhunkit W., Moser A.H., Shigenaga J.K., Grunfeld C., Feingold K.R. Endotoxin down-regulates ABCG5 and ABCG8 in mouse liver and ABCA1 and ABCG1 in J774 murine macrophages: differential role of LXR. J.Lipid Res. 2003, 44:1728-1736.
21. Koeth R.A., Wang Z., Levison B.S., Buffa J.A., Org E., Sheehy B.T., Britt E.B., Fu X., Wu Y., Li L., et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013, 19:576-585.
22. Le May C., Berger J.M., Lespine A., Pillot B., Prieur X., Letessier E., Hussain M.M., Collet X., Cariou B., Costet P. Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1. Arterioscler. Thromb. Vasc. Biol. 2013, 33:1484-1493.
23. Marshall S.M., Gromovsky A.D., Kelley K.L., Davis M.A., Wilson M.D., Lee R.G., Crooke R.M., Graham M.J., Rudel L.L., Brown J.M., Temel R.E. Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic cholesterol for fecal excretion. PLoS ONE 2014, 9:e98953.
24. Rader D.J., Tall A.R. The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis?. Nat. Med. 2012, 18:1344-1346.
25. Rader D.J., Alexander E.T., Weibel G.L., Billheimer J., Rothblat G.H. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J.Lipid Res. 2009, 50(Suppl):S189-S194.
26. Rong X., Albert C.J., Hong C., Duerr M.A., Chamberlain B.T., Tarling E.J., Ito A., Gao J., Wang B., Edwards P.A., et al. LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. Cell Metab. 2013, 18:685-697.
27. Rosenson R.S., Brewer H.B., Davidson W.S., Fayad Z.A., Fuster V., Goldstein J., Hellerstein M., Jiang X.C., Phillips M.C., Rader D.J., et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 2012, 125:1905-1919.
28. Schwartz G.G., Olsson A.G., Abt M., Ballantyne C.M., Barter P.J., Brumm J., Chaitman B.R., Holme I.M., Kallend D., Leiter L.A., et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N.Engl. J. Med. 2012, 367:2089-2099. dal-OUTCOMESInvestigators.
29. Sehayek E., Hazen S.L. Cholesterol absorption from the intestine is a major determinant of reverse cholesterol transport from peripheral tissue macrophages. Arterioscler. Thromb. Vasc. Biol. 2008, 28:1296-1297.
30. Smyth G.K. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 2004, 3. article 3.
31. Tang W.H., Wang Z., Levison B.S., Koeth R.A., Britt E.B., Fu X., Wu Y., Hazen S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N.Engl. J. Med. 2013, 368:1575-1584.
32. Temel R.E., Brown J.M. Biliary and nonbiliary contributions to reverse cholesterol transport. Curr. Opin. Lipidol. 2012, 23:85-90.
33. Temel R.E., Tang W., Ma Y., Rudel L.L., Willingham M.C., Ioannou Y.A., Davies J.P., Nilsson L.M., Yu L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J.Clin. Invest. 2007, 117:1968-1978.
34. Temel R.E., Sawyer J.K., Yu L., Lord C., Degirolamo C., McDaniel A., Marshall S., Wang N., Shah R., Rudel L.L., Brown J.M. Biliary sterol secretion is not required for macrophage reverse cholesterol transport. Cell Metab. 2010, 12:96-102.
35. Thomas G., Betters J.L., Lord C.C., Brown A.L., Marshall S., Ferguson D., Sawyer J., Davis M.A., Melchior J.T., Blume L.C., et al. The serine hydrolase ABHD6 Is a critical regulator of the metabolic syndrome. Cell Rep. 2013, 5:508-520.
36. Tontonoz P., Mangelsdorf D.J. Liver X receptor signaling pathways in cardiovascular disease. Mol. Endocrinol. 2003, 17:985-993.
37. van der Veen J.N., van Dijk T.H., Vrins C.L., van Meer H., Havinga R., Bijsterveld K., Tietge U.J., Groen A.K., Kuipers F. Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol. J.Biol. Chem. 2009, 284:19211-19219.
38. van der Velde A.E., Vrins C.L., van den Oever K., Kunne C., Oude Elferink R.P., Kuipers F., Groen A.K. Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. Gastroenterology 2007, 133:967-975.
39. Voight B.F., Peloso G.M., Orho-Melander M., Frikke-Schmidt R., Barbalic M., Jensen M.K., Hindy G., Hólm H., Ding E.L., Johnson T., et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012, 380:572-580.
40. Wang Z., Klipfell E., Bennett B.J., Koeth R., Levison B.S., Dugar B., Feldstein A.E., Britt E.B., Fu X., Chung Y.M., et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011, 472:57-63.
41. Wang Z., Tang W.H., Buffa J.A., Fu X., Britt E.B., Koeth R.A., Levison B.S., Fan Y., Wu Y., Hazen S.L. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 2014, 35:904-910.
42. Wiersma H., Gatti A., Nijstad N., Oude Elferink R.P., Kuipers F., Tietge U.J. Scavenger receptor class B type I mediates biliary cholesterol secretion independent of ATP-binding cassette transporter g5/g8 in mice. Hepatology 2009, 50:1263-1272.
43. Yu L., Hammer R.E., Li-Hawkins J., Von Bergmann K., Lutjohann D., Cohen J.C., Hobbs H.H. Disruption of Abcg5 and Abcg8 inmice reveals their crucial role in biliary cholesterol secretion. Proc. Natl. Acad. Sci. USA 2002, 99:16237-16242.