Trimethylamine N-oxide ameliorates hepatic damage including reduction of hepatic bile acids and cholesterol in Fxr-null mice

References

• Achard CS, Laybutt DR. 2012. Lipid-induced endoplasmic reticulum stress in liver cells results in two distinct outcomes: adaptation with enhanced insulin signaling or insulin resistance. Endocrinology. 153(5):2164–2177. doi: 10.1210/en.2011-1881.
   PubMed Web of Science ®Google Scholar
• Arteel GE. 2012. Beyond reasonable doubt: who is the culprit in lipotoxicity in NAFLD/NASH? Hepatology. 55(6):2030–2032. doi: 10.1002/hep.25721.
   PubMedGoogle Scholar
• Barrea L, Annunziata G, Muscogiuri G, Di Somma C, Laudisio D, Maisto M, de Alteriis G, Tenore GC, Colao A, Savastano S. 2018. Trimethylamine-N-oxide (TMAO) as Novel Potential Biomarker of Early Predictors of Metabolic Syndrome. Nutrients. 10(12)doi::1971. 3390/nu10121971 doi: 10.3390/nu10121971.
   PubMed Web of Science ®Google Scholar
• Bugianesi E. 2008. Nonalcoholic fatty liver disease (NAFLD) and cardiac lipotoxicity: another piece of the puzzle. Hepatology. 47(1):2–4. doi: 10.1002/hep.22105.
   PubMed Web of Science ®Google Scholar
• Cariou B, Staels B. 2007. FXR: a promising target for the metabolic syndrome? Trends Pharmacol Sci. 28(5):236–243. doi: 10.1016/j.tips.2007.03.002.
   PubMed Web of Science ®Google Scholar
• Chen Y-m, Liu Y, Zhou R-f, Chen X-l, Wang C, Tan X-y, Wang L-j, Zheng R-d, Zhang H-w, Ling W-h 2016. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci Rep. 6(1):19076. doi: 10.1038/srep19076.
   PubMedGoogle Scholar
• Constantino-Jonapa LA, Espinoza-Palacios Y, Escalona-Montaño AR, Hernández-Ruiz P, Amezcua-Guerra LM, Amedei A, Aguirre-García MM. 2023. Contribution of trimethylamine N-oxide (TMAO) to chronic inflammatory and degenerative diseases. Biomedicines. 11(2):431. doi: 10.3390/biomedicines11020431.
   PubMed Web of Science ®Google Scholar
• Ding L, Chang M, Guo Y, Zhang L, Xue C, Yanagita T, Zhang T, Wang Y. 2018. Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis. 17(1):286. doi: 10.1186/s12944-018-0939-6.
   PubMed Web of Science ®Google Scholar
• Dumas M-E, Rothwell AR, Hoyles L, Aranias T, Chilloux J, Calderari S, Noll EM, Péan N, Boulangé CL, Blancher C. 2017. Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity, and impaired glucose tolerance. Cell Rep. 20(1):136–148. doi: 10.1016/j.celrep.2017.06.039.
   PubMed Web of Science ®Google Scholar
• Folch J, Lees M, Sloane Stanley GH. 1957. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 226(1):497–509. doi: 10.1016/S0021-9258(18)64849-5.
   PubMed Web of Science ®Google Scholar
• Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. 2018. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 24(7):908–922. doi: 10.1038/s41591-018-0104-9.
   PubMed Web of Science ®Google Scholar
• Guerra S, Mocciaro G, Gastaldelli A. 2022. Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis. Eur J Clin Invest. 52(3):e13695. doi: 10.1111/eci.13695.
   PubMed Web of Science ®Google Scholar
• Ibrahim SH, Kohli R, Gores GJ. 2011. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. 53(2):131–140. doi: 10.1097/MPG.0b013e31822578db.
   PubMed Web of Science ®Google Scholar
• Kalavalapalli S, Leiva EG, Lomonaco R, Chi X, Shrestha S, Dillard R, Budd J, Romero JP, Li C, Bril F. 2023. Adipose tissue insulin resistance predicts the severity of liver fibrosis in patients with type 2 diabetes and NAFLD. J Clin Endocrinol Metab. 108(5):1192–1201. doi: 10.1210/clinem/dgac660.
   PubMed Web of Science ®Google Scholar
• Kim I, Morimura K, Shah Y, Yang Q, Ward JM, Gonzalez FJ. 2007. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis. 28(5):940–946. doi: 10.1093/carcin/bgl249.
   PubMed Web of Science ®Google Scholar
• Kitada H, Miyata M, Nakamura T, Tozawa A, Honma W, Shimada M, Nagata K, Sinal CJ, Guo GL, Gonzalez FJ. 2003. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J Biol Chem. 278(20):17838–17844. doi: 10.1074/jbc.M210634200.
   PubMed Web of Science ®Google Scholar
• Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 19(5):576–585. doi: 10.1038/nm.3145.
   PubMed Web of Science ®Google Scholar
• Li XS, Wang Z, Cajka T, Buffa JA, Nemet I, Hurd AG, Gu X, Skye SM, Roberts AB, Wu Y. 2018. Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight. 3(6):e99096. doi: 10.1172/jci.insight.99096.
   PubMed Web of Science ®Google Scholar
• Liu N, Meng Z, Lou G, Zhou W, Wang X, Zhang Y, Zhang L, Liu X, Yen Y, Lai L. 2012. Hepatocarcinogenesis in FXR-/- mice mimics human HCC progression that operates through HNF1alpha regulation of FXR expression. Mol Endocrinol. 26(5):775–785. doi: 10.1210/me.2011-1383.
   PubMedGoogle Scholar
• Lombardo M, Aulisa G, Marcon D, Rizzo G. 2022. The influence of animal- or plant-based diets on blood and urine trimethylamine-N-oxide (TMAO) levels in humans. Curr Nutr Rep. 11(1):56–68. doi: 10.1007/s13668-021-00387-9.
   PubMedGoogle Scholar
• Matsubara T, Li F, Gonzalez FJ. 2013. FXR signaling in the enterohepatic system. Mol Cell Endocrinol. 368(1–2):17–29. doi: 10.1016/j.mce.2012.05.004.
   PubMed Web of Science ®Google Scholar
• Miyata M, Funaki A, Fukuhara C, Sumiya Y, Sugiura Y. 2020. Taurine attenuates hepatic steatosis in a genetic model of fatty liver disease. J Toxicol Sci. 45(2):87–94. doi: 10.2131/jts.45.87.
   PubMed Web of Science ®Google Scholar
• Miyata M, Shinno K, Kinoshita T, Kinoshita Y, Sugiura Y. 2017. Fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling. J Toxicol Sci. 42(6):671–681. doi: 10.2131/jts.42.671.
   PubMed Web of Science ®Google Scholar
• Miyata M, Tanaka T, Takahashi K, Funaki A, Sugiura Y. 2021. Cholesterol-lowering effects of taurine through the reduction of ileal FXR signaling due to the alteration of ileal bile acid composition. Amino Acids. 53(10):1523–1532. doi: 10.1007/s00726-021-03068-7.
   PubMed Web of Science ®Google Scholar
• Mocciaro G, Allison M, Jenkins B, Azzu V, Huang-Doran I, Herrera-Marcos LV, Hall Z, Murgia A, Susan D, Frontini M. 2023. Non-alcoholic fatty liver disease is characterised by a reduced polyunsaturated fatty acid transport via free fatty acids and high-density lipoproteins (HDL). Mol Metab. 73:101728. doi: 10.1016/j.molmet.2023.101728.
   PubMed Web of Science ®Google Scholar
• Mocciaro G, Gastaldelli A. 2022. Obesity-related insulin resistance: the central role of adipose tissue dysfunction. Handb Exp Pharmacol. 274:145–164. doi: 10.1007/164_2021_573.
   PubMedGoogle Scholar
• Nowiński A, Ufnal M. 2018. Trimethylamine N-oxide: a harmful, protective or diagnostic marker in lifestyle diseases? Nutrition. 46:7–12. doi: 10.1016/j.nut.2017.08.001.
   PubMed Web of Science ®Google Scholar
• Parlati L, Régnier M, Guillou H, Postic C. 2021. New targets for NAFLD. JHEP Rep. 3(6):100346. doi: 10.1016/j.jhepr.2021.100346.
   PubMedGoogle Scholar
• Shen T, Shi A, Wei Y, Luo X, Xi L. 2021. Farnesoid X receptor as a promising therapeutic target for nonalcoholic fatty liver disease (NAFLD) and the current development of its agonists. Discov Med. 32(167):113–121.
   PubMed Web of Science ®Google Scholar
• Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. 2000. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell. 102(6):731–744. doi: 10.1016/s0092-8674(00)00062-3
   PubMed Web of Science ®Google Scholar
• Steinke I, Ghanei N, Govindarajulu M, Yoo S, Zhong J, Amin RH. 2020. drug discovery and development of novel therapeutics for inhibiting TMAO in models of atherosclerosis and diabetes. Front Physiol. 11:567899. doi: 10.3389/fphys.2020.567899.
   PubMed Web of Science ®Google Scholar
• Tan X, Liu Y, Long J, Chen S, Liao G, Wu S, Li C, Wang L, Ling W, Zhu H. 2019. Trimethylamine N-oxide aggravates liver steatosis through modulation of bile acid metabolism and inhibition of farnesoid X receptor signaling in nonalcoholic fatty liver disease. Mol Nutr Food Res. 63(17):e1900257. doi: 10.1002/mnfr.201900257.
   PubMed Web of Science ®Google Scholar
• Tang WHW, Li XS, Wu Y, Wang Z, Khaw K-T, Wareham NJ, Nieuwdorp M, Boekholdt SM, Hazen SL. 2021. Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study. Am Heart J. 236:80–86. doi: 10.1016/j.ahj.2021.01.020.
   PubMed Web of Science ®Google Scholar
• Theofilis P, Vordoni A, Kalaitzidis RG. 2022. Trimethylamine N-oxide levels in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Metabolites. 12(12):1243. doi: 10.3390/metabo12121243.
   PubMed Web of Science ®Google Scholar
• Tilg H, Adolph TE, Dudek M, Knolle P. 2021. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 3(12):1596–1607. doi: 10.1038/s42255-021-00501-9.
   PubMedGoogle Scholar
• Trauner M, Fuchs CD. 2022. Novel therapeutic targets for cholestatic and fatty liver disease. Gut. 71(1):194–209. doi: 10.1136/gutjnl-2021-324305.
   PubMed Web of Science ®Google Scholar
• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung Y-M. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 472(7341):57–63. doi: 10.1038/nature09922.
   PubMed Web of Science ®Google Scholar
• Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W. 2007. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res. 67(3):863–867. doi: 10.1158/0008-5472.CAN-06-1078.
   PubMed Web of Science ®Google Scholar
• Zhao Z-H, Xin F-Z, Zhou D, Xue Y-Q, Liu X-L, Yang R-X, Pan Q, Fan J-G. 2019. Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats. World J Gastroenterol. 25(20):2450–2462. doi: 10.3748/wjg.v25.i20.2450.
   PubMed Web of Science ®Google Scholar
• Zhou D, Zhang J, Xiao C, Mo C, Ding BS. 2022. Trimethylamine-N-oxide (TMAO) mediates the crosstalk between the gut microbiota and hepatic vascular niche to alleviate liver fibrosis in nonalcoholic steatohepatitis. Front Immunol. 13:964477. doi: 10.3389/fimmu.2022.964477.
   PubMed Web of Science ®Google Scholar