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P. Doherty Jr. - Welch Chair in Science","award":["Q-0022"],"award-info":[{"award-number":["Q-0022"]}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP150587"],"award-info":[{"award-number":["RP150587"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,1,28]]},"abstract":"<jats:p>\n                    Inactivating mutations in the copper transporter\n                    <jats:italic>Atp7b<\/jats:italic>\n                    result in Wilson\u2019s disease. The\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse develops hallmarks of Wilson\u2019s disease. The activity of several nuclear receptors decreased in\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography\u2013mass spectrometry and correlated with transcriptomic data.\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet,\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls.\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice fed either diet were more insulin sensitive than WT controls; however, fasted\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited hypoglycemia after administration of insulin due to an impaired glucose counterregulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, including increases in glycolytic intermediates and components of the tricarboxylic acid cycle. In addition, the active phosphorylated form of AMP kinase was significantly increased in\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice relative to WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity as well as with impaired fasting glucose production in\n                    <jats:italic>Atp7b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1914267117","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T19:55:11Z","timestamp":1578686111000},"page":"2076-2083","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Metabolic dysregulation in the\n                    <i>Atp7b<\/i>\n                    <sup>\u2212\/\u2212<\/sup>\n                    Wilson\u2019s disease mouse model"],"prefix":"10.1073","volume":"117","author":[{"given":"Clavia Ruth","family":"Wooton-Kee","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Robertson","sequence":"additional","affiliation":[{"name":"Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingning","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagireddy","family":"Putluri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Coarfa","sequence":"additional","affiliation":[{"name":"Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5151-9748","authenticated-orcid":false,"given":"David D.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-4868","authenticated-orcid":false,"given":"Alli M.","family":"Nuotio-Antar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1152\/physrev.00004.2006","article-title":"Function and regulation of human copper-transporting ATPases","volume":"87","author":"Lutsenko S.","year":"2007","unstructured":"S. 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Nutr."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jhep.2011.05.030","article-title":"High fructose feeding induces copper deficiency in Sprague-Dawley rats: A novel mechanism for obesity related fatty liver","volume":"56","author":"Song M.","year":"2012","unstructured":"M. Song ., High fructose feeding induces copper deficiency in Sprague-Dawley rats: A novel mechanism for obesity related fatty liver. J. Hepatol. 56, 433\u2013440 (2012).","journal-title":"J. Hepatol."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/oby.20380","article-title":"Modest fructose beverage intake causes liver injury and fat accumulation in marginal copper deficient rats","volume":"21","author":"Song M.","year":"2013","unstructured":"M. Song ., Modest fructose beverage intake causes liver injury and fat accumulation in marginal copper deficient rats. 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Wewn."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.hepres.2004.10.009","article-title":"Liver cirrhosis and metabolism (sugar, protein, fat and trace elements)","volume":"30","author":"Arakawa Y.","year":"2004","unstructured":"Y. Arakawa, M. Moriyama, Y. Arakawa, Liver cirrhosis and metabolism (sugar, protein, fat and trace elements). Hepatol. Res. 30S, 46\u201358 (2004).","journal-title":"Hepatol. Res."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1002\/hep.22252","article-title":"Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor","volume":"47","author":"Lin H. Y.","year":"2008","unstructured":"H. Y. Lin ., Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 47, 1924\u20131935 (2008).","journal-title":"Hepatology"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2147\/JHC.S48956","article-title":"The androgen receptor as an emerging target in hepatocellular carcinoma","volume":"2","author":"Kanda T.","year":"2015","unstructured":"T. Kanda, O. Yokosuka, The androgen receptor as an emerging target in hepatocellular carcinoma. J. Hepatocell. Carcinoma 2, 91\u201399 (2015).","journal-title":"J. Hepatocell. Carcinoma"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1096\/fj.11-195701","article-title":"Glucocorticoid receptor mediates the gluconeogenic activity of the farnesoid X receptor in the fasting condition","volume":"26","author":"Renga B.","year":"2012","unstructured":"B. Renga ., Glucocorticoid receptor mediates the gluconeogenic activity of the farnesoid X receptor in the fasting condition. FASEB J. 26, 3021\u20133031 (2012).","journal-title":"FASEB J."},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1113\/jphysiol.2006.108944","article-title":"AMP-activated protein kinase: Development of the energy sensor concept","volume":"574","author":"Hardie D. G.","year":"2006","unstructured":"D. G. Hardie, S. A. Hawley, J. W. Scott, AMP-activated protein kinase: Development of the energy sensor concept. J. Physiol. 574, 7\u201315 (2006).","journal-title":"J. Physiol."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1006\/bbrc.2001.5544","article-title":"The regulation of AMP-activated protein kinase by H(2)O(2)","volume":"287","author":"Choi S. L.","year":"2001","unstructured":"S. L. Choi ., The regulation of AMP-activated protein kinase by H(2)O(2). Biochem. Biophys. Res. Commun. 287, 92\u201397 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bcp.2006.03.021","article-title":"Critical roles of AMP-activated protein kinase in the carcinogenic metal-induced expression of VEGF and HIF-1 proteins in DU145 prostate carcinoma","volume":"72","author":"Lee M.","year":"2006","unstructured":"M. Lee ., Critical roles of AMP-activated protein kinase in the carcinogenic metal-induced expression of VEGF and HIF-1 proteins in DU145 prostate carcinoma. Biochem. Pharmacol. 72, 91\u2013103 (2006).","journal-title":"Biochem. Pharmacol."},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00125-011-2326-y","article-title":"AMP-activated protein kinase mediates effects of oxidative stress on embryo gene expression in a mouse model of diabetic embryopathy","volume":"55","author":"Wu Y.","year":"2012","unstructured":"Y. Wu, M. Viana, S. Thirumangalathu, M. R. 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Hepatology 50, 1204\u20131216 (2009).","journal-title":"Hepatology"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1074\/jbc.274.9.5692","article-title":"Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion","volume":"274","author":"Chavin K. D.","year":"1999","unstructured":"K. D. Chavin ., Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J. Biol. Chem. 274, 5692\u20135700 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1093\/bioinformatics\/btq466","article-title":"ChEA: Transcription factor regulation inferred from integrating genome-wide ChIP-X experiments","volume":"26","author":"Lachmann A.","year":"2010","unstructured":"A. Lachmann ., ChEA: Transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. 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Ye ., Hepatocyte nuclear factor 3\/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues. Mol. Cell. Biol. 17, 1626\u20131641 (1997).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/hmg\/8.9.1665","article-title":"Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation","volume":"8","author":"Buiakova O. I.","year":"1999","unstructured":"O. I. Buiakova ., Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation. Hum. Mol. Genet. 8, 1665\u20131671 (1999).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_4_49_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council, Guide for the Care and Use of Laboratory Animals (National Academies Press, Washington, DC, ed. 8, 2011).","edition":"8"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"E1517","DOI":"10.1152\/ajpendo.00522.2007","article-title":"Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice","volume":"293","author":"Nuotio-Antar A. M.","year":"2007","unstructured":"A. M. Nuotio-Antar, D. L. Hachey, A. H. Hasty, Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice. Am. J. Physiol. Endocrinol. Metab. 293, E1517\u2013E1528 (2007).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2337\/db09-1471","article-title":"A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes","volume":"59","author":"Butler A. A.","year":"2010","unstructured":"A. A. Butler, L. P. Kozak, A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 59, 323\u2013329 (2010).","journal-title":"Diabetes"},{"key":"e_1_3_4_52_2","unstructured":"C. R. Wooton-Kee C. Coarfa M. Robertson Gene expression in wild type and Atp7b \u2212\/\u2212 mice. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?&acc=GSE125637. 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