{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:23:49Z","timestamp":1790389429879,"version":"4.1.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Heart Foundation","award":["2007T046"],"award-info":[{"award-number":["2007T046"]}]},{"name":"Innovational Research Incentives Scheme\u00a0program of the Netherlands Organization for Scientific Research","award":["VENI 916.10.117"],"award-info":[{"award-number":["VENI 916.10.117"]}]},{"name":"Innovational Research Incentives Scheme\u00a0program of the Netherlands Organization for Scientific Research","award":["VIDI 917.13.350"],"award-info":[{"award-number":["VIDI 917.13.350"]}]},{"name":"European Research Council","award":["311549"],"award-info":[{"award-number":["311549"]}]},{"name":"Swedish Science Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathological cardiac hypertrophy is characterized by a shift in metabolic substrate utilization from fatty acids to glucose, but the molecular events underlying the metabolic remodeling remain poorly understood. Here, we investigated the role of liver X receptors (LXRs), which are key regulators of glucose and lipid metabolism, in cardiac hypertrophic pathogenesis. Using a transgenic approach in mice, we show that overexpression of LXR\u03b1 acts to protect the heart against hypertrophy, fibrosis, and dysfunction. Gene expression profiling studies revealed that genes regulating metabolic pathways were differentially expressed in hearts with elevated LXR\u03b1. Functionally, LXR\u03b1 overexpression in isolated cardiomyocytes and murine hearts markedly enhanced the capacity for myocardial glucose uptake following hypertrophic stress. Conversely, this adaptive response was diminished in LXR\u03b1\u2010deficient mice. Transcriptional changes induced by LXR\u03b1 overexpression promoted energy\u2010independent utilization of glucose via the hexosamine biosynthesis pathway, resulting in O\u2010GlcNAc modification of GATA4 and Mef2c and the induction of cytoprotective natriuretic peptide expression. Our results identify LXR\u03b1 as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to chronic cardiac stress, and suggest that modulating LXR\u03b1 may provide a unique opportunity for intervening in myocyte metabolism.<\/jats:p>","DOI":"10.15252\/emmm.201404669","type":"journal-article","created":{"date-parts":[[2015,7,9]],"date-time":"2015-07-09T21:40:43Z","timestamp":1436478043000},"page":"1229-1243","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Cardiac LXR\u03b1 protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization"],"prefix":"10.1038","volume":"7","author":[{"given":"Megan V","family":"Cannon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman HW","family":"Sillj\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen WA","family":"Sijbesma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Vreeswijk\u2010Baudoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolita","family":"Ciapaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"van der Sluis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Deursen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo JJ","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J","family":"de Windt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010\u00c5ke","family":"Gustafsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiek H","family":"van Gilst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"BFEMMM201404669_CR1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1172\/JCI9794","volume":"107","author":"S Alberti","year":"2001","unstructured":"Alberti S, Schuster G, Parini P, Feltkamp D, Diczfalusy U, Rudling M, Angelin B, Bjorkhem I, Pettersson S, Gustafsson JA (2001) Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta\u2010deficient mice. J Clin Invest 107: 565\u2013573","journal-title":"J Clin Invest"},{"key":"BFEMMM201404669_CR2","first-page":"H742","volume":"267","author":"MF Allard","year":"1994","unstructured":"Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD (1994) Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 267: H742\u2013H750","journal-title":"Am J Physiol"},{"key":"BFEMMM201404669_CR3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/eurjhf\/hfr173","volume":"14","author":"H Ardehali","year":"2012","unstructured":"Ardehali H, Sabbah HN, Burke MA, Sarma S, Liu PP, Cleland JG, Maggioni A, Fonarow GC, Abel ED, Campia U et\u00a0al (2012) Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail 14: 120\u2013129","journal-title":"Eur J Heart Fail"},{"key":"BFEMMM201404669_CR4","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1053\/j.gastro.2010.11.053","volume":"140","author":"SW Beaven","year":"2011","unstructured":"Beaven SW, Wroblewski K, Wang J, Hong C, Bensinger S, Tsukamoto H, Tontonoz P (2011) Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease. Gastroenterology 140: 1052\u20131062","journal-title":"Gastroenterology"},{"key":"BFEMMM201404669_CR5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","volume":"435","author":"MD Brand","year":"2011","unstructured":"Brand MD, Nicholls DG (2011) Assessing mitochondrial dysfunction in cells. Biochem J 435: 297\u2013312","journal-title":"Biochem J"},{"key":"BFEMMM201404669_CR6","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1093\/eurheartj\/eht066","volume":"34","author":"FP Brouwers","year":"2013","unstructured":"Brouwers FP, de Boer RA, van der Harst P, Voors AA, Gansevoort RT, Bakker SJ, Hillege HL, van Veldhuisen DJ, van Gilst WH (2013) Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community\u2010based cohort: 11\u2010year follow\u2010up of PREVEND. Eur Heart J 34: 1424\u20131431","journal-title":"Eur Heart J"},{"key":"BFEMMM201404669_CR7","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1194\/jlr.M500157-JLR200","volume":"46","author":"M Chen","year":"2005","unstructured":"Chen M, Beaven S, Tontonoz P (2005) Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha. J Lipid Res 46: 2570\u20132579","journal-title":"J Lipid Res"},{"key":"BFEMMM201404669_CR8","doi-asserted-by":"crossref","first-page":"48283","DOI":"10.1074\/jbc.M302287200","volume":"278","author":"KT Dalen","year":"2003","unstructured":"Dalen KT, Ulven SM, Bamberg K, Gustafsson JA, Nebb HI (2003) Expression\u00a0of the insulin\u2010responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha. J Biol Chem 278: 48283\u201348291","journal-title":"J Biol Chem"},{"key":"BFEMMM201404669_CR9","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.yjmcc.2011.08.009","volume":"52","author":"VM Darley\u2010Usmar","year":"2012","unstructured":"Darley\u2010Usmar VM, Ball LE, Chatham JC (2012) Protein O\u2010linked beta\u2010N\u2010acetylglucosamine: a novel effector of cardiomyocyte metabolism and function. J Mol Cell Cardiol 52: 538\u2013549","journal-title":"J Mol Cell Cardiol"},{"key":"BFEMMM201404669_CR10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/CIRCRESAHA.113.300376","volume":"113","author":"T Doenst","year":"2013","unstructured":"Doenst T, Nguyen TD, Abel ED (2013) Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res 113: 709\u2013724","journal-title":"Circ Res"},{"key":"BFEMMM201404669_CR11","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.yjmcc.2009.11.017","volume":"48","author":"AA Domenighetti","year":"2010","unstructured":"Domenighetti AA, Danes VR, Curl CL, Favaloro JM, Proietto J, Delbridge LM (2010) Targeted GLUT\u20104 deficiency in the heart induces cardiomyocyte hypertrophy and impaired contractility linked with Ca(2\u00a0+\u00a0) and proton flux dysregulation. J Mol Cell Cardiol 48: 663\u2013672","journal-title":"J Mol Cell Cardiol"},{"key":"BFEMMM201404669_CR12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.physiol.65.092101.142243","volume":"65","author":"N Frey","year":"2003","unstructured":"Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65: 45\u201379","journal-title":"Annu Rev Physiol"},{"key":"BFEMMM201404669_CR13","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1093\/eurheartj\/ehr136","volume":"33","author":"C Giannarelli","year":"2012","unstructured":"Giannarelli C, Cimmino G, Connolly TM, Ibanez B, Ruiz JM, Alique M, Zafar MU, Fuster V, Feuerstein G, Badimon JJ (2012) Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: an magnetic resonance imaging study in a model of advanced atherosclerosis. Eur Heart J 33: 264\u2013273","journal-title":"Eur Heart J"},{"key":"BFEMMM201404669_CR14","doi-asserted-by":"crossref","first-page":"800","DOI":"10.2337\/db09-1542","volume":"59","author":"BA Griesel","year":"2010","unstructured":"Griesel BA, Weems J, Russell RA, Abel ED, Humphries K, Olson AL (2010) Acute inhibition of fatty acid import inhibits GLUT4 transcription in adipose tissue, but not skeletal or cardiac muscle tissue, partly through liver X receptor (LXR) signaling. Diabetes 59: 800\u2013807","journal-title":"Diabetes"},{"key":"BFEMMM201404669_CR15","doi-asserted-by":"crossref","first-page":"9180","DOI":"10.1016\/S0021-9258(18)31568-0","volume":"266","author":"J Gulick","year":"1991","unstructured":"Gulick J, Subramaniam A, Neumann J, Robbins J (1991) Isolation and characterization of the mouse cardiac myosin heavy chain genes. J Biol Chem 266: 9180\u20139185","journal-title":"J Biol Chem"},{"key":"BFEMMM201404669_CR16","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/j.1755-5922.2010.00152.x","volume":"29","author":"S Hayek","year":"2011","unstructured":"Hayek S, Nemer M (2011) Cardiac natriuretic peptides: from basic discovery to clinical practice. Cardiovasc Ther 29: 362\u2013376","journal-title":"Cardiovasc Ther"},{"key":"BFEMMM201404669_CR17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1172\/JCI17061","volume":"111","author":"R Holtwick","year":"2003","unstructured":"Holtwick R, van Eickels M, Skryabin BV, Baba HA, Bubikat A, Begrow F, Schneider MD, Garbers DL, Kuhn M (2003) Pressure\u2010independent cardiac hypertrophy in mice with cardiomyocyte\u2010restricted inactivation of the atrial natriuretic peptide receptor guanylyl cyclase\u2010A. J Clin Invest 111: 1399\u20131407","journal-title":"J Clin Invest"},{"key":"BFEMMM201404669_CR18","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ymgme.2004.07.007","volume":"83","author":"KA Houck","year":"2004","unstructured":"Houck KA, Borchert KM, Hepler CD, Thomas JS, Bramlett KS, Michael LF, Burris TP (2004) T0901317 is a dual LXR\/FXR agonist. Mol Genet Metab 83: 184\u2013187","journal-title":"Mol Genet Metab"},{"key":"BFEMMM201404669_CR19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nm820","volume":"9","author":"SB Joseph","year":"2003","unstructured":"Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P (2003) Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 9: 213\u2013219","journal-title":"Nat Med"},{"key":"BFEMMM201404669_CR20","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.2337\/diabetes.54.4.1108","volume":"54","author":"ET Kase","year":"2005","unstructured":"Kase ET, Wensaas AJ, Aas V, Hojlund K, Levin K, Thoresen GH, Beck\u2010Nielsen H, Rustan AC, Gaster M (2005) Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway. Diabetes 54: 1108\u20131115","journal-title":"Diabetes"},{"key":"BFEMMM201404669_CR21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/377151a0","volume":"377","author":"EB Katz","year":"1995","unstructured":"Katz EB, Stenbit AE, Hatton K, DePinho R, Charron MJ (1995) Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377: 151\u2013155","journal-title":"Nature"},{"key":"BFEMMM201404669_CR22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/cvr\/cvr071","volume":"90","author":"SC Kolwicz Jr","year":"2011","unstructured":"Kolwicz SC Jr, Tian R (2011) Glucose metabolism and cardiac hypertrophy. Cardiovasc Res 90: 194\u2013201","journal-title":"Cardiovasc Res"},{"key":"BFEMMM201404669_CR23","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1161\/CIRCRESAHA.113.302095","volume":"113","author":"SC Kolwicz Jr","year":"2013","unstructured":"Kolwicz SC Jr, Purohit S, Tian R (2013) Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res 113: 603\u2013616","journal-title":"Circ Res"},{"key":"BFEMMM201404669_CR24","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1093\/eurjhf\/hfq109","volume":"12","author":"I Kuipers","year":"2010","unstructured":"Kuipers I, Li J, Vreeswijk\u2010Baudoin I, Koster J, van der Harst P, Sillje HH, Kuipers F, van Veldhuisen DJ, van Gilst WH, de Boer RA (2010) Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in\u00a0vivo. Eur J Heart Fail 12: 1042\u20131050","journal-title":"Eur J Heart Fail"},{"key":"BFEMMM201404669_CR25","volume-title":"Probe Reports from the NIH Molecular Libraries Program","author":"N Kumar","year":"2010","unstructured":"Kumar N, Solt LA, Conkright J, Wang Y, Istrate MA, Busby SA, Garcia\u2010Ordonez RD, Nuhant P, Burris T, Mercer BA et\u00a0al (2010) Campaign to Identify Novel Modulators of the Retinoic Acid Receptor\u2010Related Orphan Receptors (ROR). In Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US)"},{"key":"BFEMMM201404669_CR26","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1073\/pnas.0830671100","volume":"100","author":"BA Laffitte","year":"2003","unstructured":"Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL et\u00a0al (2003) Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 100: 5419\u20135424","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201404669_CR27","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/sj.bjp.0707241","volume":"151","author":"CE Leik","year":"2007","unstructured":"Leik CE, Carson NL, Hennan JK, Basso MD, Liu QY, Crandall DL, Nambi P (2007) GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II\u2010mediated pressor responses in Sprague\u2010Dawley rats. Br J Pharmacol 151: 450\u2013456","journal-title":"Br J Pharmacol"},{"key":"BFEMMM201404669_CR28","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1161\/01.CIR.0000034049.61181.F3","volume":"106","author":"R Liao","year":"2002","unstructured":"Liao R, Jain M, Cui L, D'Agostino J, Aiello F, Luptak I, Ngoy S, Mortensen RM, Tian R (2002) Cardiac\u2010specific overexpression of GLUT1 prevents the development of heart failure attributable to pressure overload in mice. Circulation 106: 2125\u20132131","journal-title":"Circulation"},{"key":"BFEMMM201404669_CR29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1152\/physiolgenomics.00148.2011","volume":"44","author":"B Lu","year":"2012","unstructured":"Lu B, Yu H, Zwartbol M, Ruifrok WP, van Gilst WH, de Boer RA, Sillje HH (2012) Identification of hypertrophy\u2010 and heart failure\u2010associated genes by combining in\u00a0vitro and in\u00a0vivo models. Physiol Genomics 44: 443\u2013454","journal-title":"Physiol Genomics"},{"key":"BFEMMM201404669_CR30","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1161\/CIRCULATIONAHA.105.534594","volume":"112","author":"I Luptak","year":"2005","unstructured":"Luptak I, Balschi JA, Xing Y, Leone TC, Kelly DP, Tian R (2005) Decreased contractile and metabolic reserve in peroxisome proliferator\u2010activated receptor\u2010alpha\u2010null hearts can be rescued by increasing glucose transport and utilization. Circulation 112: 2339\u20132346","journal-title":"Circulation"},{"key":"BFEMMM201404669_CR31","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.febslet.2007.03.047","volume":"581","author":"N Mitro","year":"2007","unstructured":"Mitro N, Vargas L, Romeo R, Koder A, Saez E (2007) T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR. FEBS Lett 581: 1721\u20131726","journal-title":"FEBS Lett"},{"key":"BFEMMM201404669_CR32","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1172\/JCI24594","volume":"115","author":"F Morello","year":"2005","unstructured":"Morello F, de Boer RA, Steffensen KR, Gnecchi M, Chisholm JW, Boomsma F, Anderson LM, Lawn RM, Gustafsson JA, Lopez\u2010Ilasaca M et\u00a0al (2005) Liver X receptors alpha and beta regulate renin expression in\u00a0vivo. J Clin Invest 115: 1913\u20131922","journal-title":"J Clin Invest"},{"key":"BFEMMM201404669_CR33","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1093\/emboj\/19.9.2046","volume":"19","author":"S Morin","year":"2000","unstructured":"Morin S, Charron F, Robitaille L, Nemer M (2000) GATA\u2010dependent recruitment of MEF2 proteins to target promoters. EMBO J 19: 2046\u20132055","journal-title":"EMBO J"},{"key":"BFEMMM201404669_CR34","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1161\/CIRCULATIONAHA.105.560177","volume":"113","author":"SU Naik","year":"2006","unstructured":"Naik SU, Wang X, Da Silva JS, Jaye M, Macphee CH, Reilly MP, Billheimer JT, Rothblat GH, Rader DJ (2006) Pharmacological activation of liver X receptors promotes reverse cholesterol transport in\u00a0vivo. Circulation 113: 90\u201397","journal-title":"Circulation"},{"key":"BFEMMM201404669_CR35","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJMra063052","volume":"356","author":"S Neubauer","year":"2007","unstructured":"Neubauer S (2007) The failing heart\u2013an engine out of fuel. N Engl J Med 356: 1140\u20131151","journal-title":"N Engl J Med"},{"key":"BFEMMM201404669_CR36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1161\/CIRCRESAHA.110.224675","volume":"107","author":"GA Ngoh","year":"2010","unstructured":"Ngoh GA, Facundo HT, Zafir A, Jones SP (2010) O\u2010GlcNAc signaling in the cardiovascular system. Circ Res 107: 171\u2013185","journal-title":"Circ Res"},{"key":"BFEMMM201404669_CR37","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cardiores.2005.10.001","volume":"69","author":"T Nishikimi","year":"2006","unstructured":"Nishikimi T, Maeda N, Matsuoka H (2006) The role of natriuretic peptides in cardioprotection. Cardiovasc Res 69: 318\u2013328","journal-title":"Cardiovasc Res"},{"key":"BFEMMM201404669_CR38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1042\/bj20021665","volume":"371","author":"H Oberkofler","year":"2003","unstructured":"Oberkofler H, Schraml E, Krempler F, Patsch W (2003) Potentiation of liver X receptor transcriptional activity by peroxisome\u2010proliferator\u2010activated receptor gamma co\u2010activator 1 alpha. Biochem J 371: 89\u201396","journal-title":"Biochem J"},{"key":"BFEMMM201404669_CR39","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.jacc.2009.07.024","volume":"54","author":"LH Opie","year":"2009","unstructured":"Opie LH, Knuuti J (2009) The adrenergic\u2010fatty acid load in heart failure. J Am Coll Cardiol 54: 1637\u20131646","journal-title":"J Am Coll Cardiol"},{"key":"BFEMMM201404669_CR40","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0959-437X(98)80013-0","volume":"8","author":"DJ Peet","year":"1998","unstructured":"Peet DJ, Janowski BA, Mangelsdorf DJ (1998) The LXRs: a new class of oxysterol receptors. Curr Opin Genet Dev 8: 571\u2013575","journal-title":"Curr Opin Genet Dev"},{"key":"BFEMMM201404669_CR41","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.1128\/MCB.22.16.5989-5999.2002","volume":"22","author":"SE Ross","year":"2002","unstructured":"Ross SE, Erickson RL, Gerin I, DeRose PM, Bajnok L, Longo KA, Misek DE, Kuick R, Hanash SM, Atkins KB et\u00a0al (2002) Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor alpha in adipocyte metabolism. Mol Cell Biol 22: 5989\u20135999","journal-title":"Mol Cell Biol"},{"key":"BFEMMM201404669_CR42","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1161\/01.CIR.0000026802.79202.96","volume":"106","author":"GU Schuster","year":"2002","unstructured":"Schuster GU, Parini P, Wang L, Alberti S, Steffensen KR, Hansson GK, Angelin B, Gustafsson JA (2002) Accumulation of foam cells in liver X receptor\u2010deficient mice. Circulation 106: 1147\u20131153","journal-title":"Circulation"},{"key":"BFEMMM201404669_CR43","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1152\/physrev.00006.2004","volume":"85","author":"WC Stanley","year":"2005","unstructured":"Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85: 1093\u20131129","journal-title":"Physiol Rev"},{"key":"BFEMMM201404669_CR44","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1681\/ASN.2012010022","volume":"23","author":"H Tachibana","year":"2012","unstructured":"Tachibana H, Ogawa D, Matsushita Y, Bruemmer D, Wada J, Teshigawara S, Eguchi J, Sato\u2010Horiguchi C, Uchida HA, Shikata K et\u00a0al (2012) Activation of liver X receptor inhibits osteopontin and ameliorates diabetic nephropathy. J Am Soc Nephrol 23: 1835\u20131846","journal-title":"J Am Soc Nephrol"},{"key":"BFEMMM201404669_CR45","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.1073\/pnas.070371497","volume":"97","author":"N Tamura","year":"2000","unstructured":"Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasahara M, Hashimoto R, Katsuura G, Mukoyama M et\u00a0al (2000) Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci USA 97: 4239\u20134244","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201404669_CR46","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1210\/me.2003-0061","volume":"17","author":"P Tontonoz","year":"2003","unstructured":"Tontonoz P, Mangelsdorf DJ (2003) Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 17: 985\u2013993","journal-title":"Mol Endocrinol"},{"key":"BFEMMM201404669_CR47","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.bbamcr.2010.09.006","volume":"1813","author":"R Ventura\u2010Clapier","year":"2011","unstructured":"Ventura\u2010Clapier R, Garnier A, Veksler V, Joubert F (2011) Bioenergetics of the failing heart. Biochim Biophys Acta 1813: 1360\u20131372","journal-title":"Biochim Biophys Acta"},{"key":"BFEMMM201404669_CR48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/s00395-011-0236-2","volume":"107","author":"J Voelkl","year":"2012","unstructured":"Voelkl J, Lin Y, Alesutan I, Ahmed MS, Pasham V, Mia S, Gu S, Feger M, Saxena A, Metzler B et\u00a0al (2012) Sgk1 sensitivity of Na(+)\/H(+) exchanger activity and cardiac remodeling following pressure overload. Basic Res Cardiol 107: 236","journal-title":"Basic Res Cardiol"},{"key":"BFEMMM201404669_CR49","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1006\/jmcc.1998.0804","volume":"31","author":"RB Wambolt","year":"1999","unstructured":"Wambolt RB, Henning SL, English DR, Dyachkova Y, Lopaschuk GD, Allard MF (1999) Glucose utilization and glycogen turnover are accelerated in hypertrophied rat hearts during severe low\u2010flow ischemia. J Mol Cell Cardiol 31: 493\u2013502","journal-title":"J Mol Cell Cardiol"},{"key":"BFEMMM201404669_CR50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1161\/01.HYP.0000074905.22908.A6","volume":"42","author":"D Wang","year":"2003","unstructured":"Wang D, Oparil S, Feng JA, Li P, Perry G, Chen LB, Dai M, John SW, Chen YF (2003) Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide\u2010null mouse. Hypertension 42: 88\u201395","journal-title":"Hypertension"},{"key":"BFEMMM201404669_CR51","doi-asserted-by":"crossref","first-page":"17797","DOI":"10.1073\/pnas.1001907107","volume":"107","author":"LJ Watson","year":"2010","unstructured":"Watson LJ, Facundo HT, Ngoh GA, Ameen M, Brainard RE, Lemma KM, Long BW, Prabhu SD, Xuan YT, Jones SP (2010) O\u2010linked beta\u2010N\u2010acetylglucosamine transferase is indispensable in the failing heart. Proc Natl Acad Sci USA 107: 17797\u201317802","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201404669_CR52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jacc.2007.10.021","volume":"51","author":"RM Witteles","year":"2008","unstructured":"Witteles RM, Fowler MB (2008) Insulin\u2010resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol 51: 93\u2013102","journal-title":"J Am Coll Cardiol"},{"key":"BFEMMM201404669_CR53","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/cvr\/cvp180","volume":"84","author":"S Wu","year":"2009","unstructured":"Wu S, Yin R, Ernest R, Li Y, Zhelyabovska O, Luo J, Yang Y, Yang Q (2009) Liver X receptors are negative regulators of cardiac hypertrophy\u00a0via suppressing NF\u2010kappaB signalling. Cardiovasc Res 84: 119\u2013126","journal-title":"Cardiovasc Res"},{"key":"BFEMMM201404669_CR54","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCHEARTFAILURE.112.971168","volume":"6","author":"L Yu","year":"2013","unstructured":"Yu L, Ruifrok WP, Meissner M, Bos EM, van Goor H, Sanjabi B, van der Harst P, Pitt B, Goldstein IJ, Koerts JA et\u00a0al (2013) Genetic and pharmacological inhibition of galectin\u20103 prevents cardiac remodeling\u00a0by\u00a0interfering with myocardial fibrogenesis. Circ Heart Fail 6: 107\u2013117","journal-title":"Circ Heart Fail"},{"key":"BFEMMM201404669_CR55","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1172\/JCI27883","volume":"116","author":"N Zelcer","year":"2006","unstructured":"Zelcer N, Tontonoz P (2006) Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 116: 607\u2013614","journal-title":"J Clin Invest"},{"key":"BFEMMM201404669_CR56","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1172\/JCI59817","volume":"122","author":"Y Zhang","year":"2012","unstructured":"Zhang Y, Breevoort SR, Angdisen J, Fu M, Schmidt DR, Holmstrom SR, Kliewer SA, Mangelsdorf DJ, Schulman IG (2012) Liver LXRalpha\u00a0expression is crucial for whole body cholesterol homeostasisand reverse cholesterol transport in mice. J Clin Invest 122: 1688\u20131699","journal-title":"J Clin Invest"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201404669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.201404669","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.201404669\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.201404669","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201404669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:10:51Z","timestamp":1779084651000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.201404669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,14]]},"references-count":56,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9,1]]}},"alternative-id":["BFEMMM201404669"],"URL":"https:\/\/doi.org\/10.15252\/emmm.201404669","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,14]]},"assertion":[{"value":"19 September 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}