Branched-chain amino acids promote hepatic Cyp7a1 expression and bile acid synthesis via suppressing FGF21-ERK pathway

White PJ, Newgard CB. Branched-chain amino acids in disease. Science. 2019;363:582–3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ericksen RE, Lim SL, McDonnell E, Shuen WH, Vadiveloo M, White PJ, et al. Loss of BCAA catabolism during carcinogenesis enhances mTORC1 activity and promotes tumor development and progression. Cell Metab. 2019;29:1151–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu G, Sun H, She P, Youn JY, Warburton S, Ping P, et al. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. J Clin Invest. 2009;119:1678–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

White PJ, McGarrah RW, Grimsrud PA, Tso SC, Yang WH, Haldeman JM, et al. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Cell Metab. 2018;27:1281–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, et al. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11:e002157.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Y, Huang K, Liu F, Lu X, Huang J, Gu D. Association of circulating branched-chain amino acids with risk of cardiovascular disease: A systematic review and meta-analysis. Atherosclerosis. 2022;350:90–6.

Article  CAS  PubMed  Google Scholar 

McGarrah RW, White PA-OX. Branched-chain amino acids in cardiovascular disease. Nat Rev Cardiol. 2023;20:77–89.

Article  CAS  PubMed  Google Scholar 

Zhao Y, Dai XY, Zhou Z, Zhao GX, Wang X, Xu MJ. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacol Sin. 2016;37:196–203.

Article  CAS  PubMed  Google Scholar 

Xu Y, Jiang H, Li L, Chen F, Liu Y, Zhou M, et al. Branched-chain amino acid catabolism promotes thrombosis risk by enhancing tropomodulin-3 propionylation in platelets. Circulation. 2020;142:49–64.

Article  CAS  PubMed  Google Scholar 

Hu W, Liu Z, Yu W, Wen S, Wang X, Qi X, et al. Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease. Ann Med. 2021;53:1316–26.

Article  PubMed  Google Scholar 

Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2013;11:55–67.

Article  PubMed  Google Scholar 

Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006;439:484–9.

Article  CAS  PubMed  Google Scholar 

de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013;17:657–69.

Article  PubMed  PubMed Central  Google Scholar 

Castellanos-Jankiewicz A, Guzmán-Quevedo O, Fénelon VS, Zizzari P, Quarta C, Bellocchio L, et al. Hypothalamic bile acid-TGR5 signaling protects from obesity. Cell Metab. 2021;33:1483–92.

Article  CAS  PubMed  Google Scholar 

Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile-acid signalling for metabolic diseases. Nat Rev Drug Discov. 2008;7:678–93.

Article  CAS  PubMed  Google Scholar 

Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65:2461–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217–25.

Article  CAS  PubMed  Google Scholar 

Song KH, Li T, Owsley E, Strom S, Chiang JY. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology. 2009;49:297–305.

Article  CAS  PubMed  Google Scholar 

Shin DJ, Osborne TF. FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. J Biol Chem. 2009;284:11110–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kong B, Wang L, Chiang JY, Zhang Y, Klaassen CD, Guo GL. Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology. 2012;56:1034–43.

Article  CAS  PubMed  Google Scholar 

Henkel AS, LeCuyer B, Olivares S, Green RM. Endoplasmic reticulum stress regulates hepatic bile acid metabolism in mice. Cell Mol Gastroenterol Hepatol. 2016;3:261–71.

Article  PubMed  PubMed Central  Google Scholar 

Sniderman AD, Glavinovic T, Thanassoulis G. Key questions about familial hypercholesterolemia: JACC review topic of the week. J Am Coll Cardiol. 2022;79:1023–31.

Article  CAS  PubMed  Google Scholar 

Soehnlein O, Swirski FK. Hypercholesterolemia links hematopoiesis with atherosclerosis. Trends Endocrinol Metab. 2013;24:129–36.

Article  CAS  PubMed  Google Scholar 

Li T, Owsley E, Matozel M, Hsu P, Novak CM, Chiang JY. Transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevents high-fat diet-induced obesity and insulin resistance in mice. Hepatology. 2010;52:678–90.

Article  CAS  PubMed  Google Scholar 

Miyake JH, Duong-Polk XT, Taylor JM, Du EZ, Castellani LW, Lusis AJ, et al. Transgenic expression of cholesterol-7-alpha-hydroxylase prevents atherosclerosis in C57BL/6J mice. Arterioscler Thromb Vasc Biol. 2002;22:121–6.

Article  CAS  PubMed  Google Scholar 

Pullinger CR, Eng C, Salen G, Shefer S, Batta AK, Erickson SK, et al. Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest. 2002;110:109–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin HA-O, An Y, Tang HA-O, Wang Y. Alterations of bile acids and gut microbiota in obesity induced by high fat diet in rat model. J Agric Food Chem. 2019;67:3624–32.

Article  CAS  PubMed  Google Scholar 

Yu C, Wang F, Kan M, Jin C, Jones RB, Weinstein M, et al. Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J Biol Chem. 2000;275:15482–9.

Article  CAS  PubMed  Google Scholar 

Wang C, Chen Z, Li S, Zhang Y, Jia S, Li J, et al. Hepatic overexpression of ATP synthase β subunit activates PI3K/Akt pathway to ameliorate hyperglycemia of diabetic mice. Diabetes 2014;63:947–59.

Article  CAS  PubMed  Google Scholar 

Jones RD, Repa JJ, Russell DW, Dietschy JM, Turley SD. Delineation of biochemical, molecular, and physiological changes accompanying bile acid pool size restoration in Cyp7a1−/− mice fed low levels of cholic acid. Am J Physiol Gastrointest Liver Physiol. 2012;303:G263–74.

Article  CAS  PubMed 

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