{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:21:20Z","timestamp":1792592480180,"version":"4.5.0"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["T.0141.19"],"award-info":[{"award-number":["T.0141.19"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["J.0119.22"],"award-info":[{"award-number":["J.0119.22"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002910","name":"F\u00e9d\u00e9ration Wallonie-Bruxelles","doi-asserted-by":"publisher","award":["22\/27-122"],"award-info":[{"award-number":["22\/27-122"]}],"id":[{"id":"10.13039\/501100002910","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In <jats:italic>Alms1<\/jats:italic>-mutant mice (<jats:italic>foz\/foz<\/jats:italic>) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>According to previous studies, 12 weeks of HFD induced NASH in all <jats:italic>foz\/foz<\/jats:italic> mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.1051157","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T05:40:02Z","timestamp":1668577202000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations"],"prefix":"10.3389","volume":"9","author":[{"given":"Camille","family":"Pichon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Nachit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Gillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greetje","family":"Vande Velde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Lanthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle A.","family":"Leclercq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease \u2013 A global public health perspective.","volume":"70","author":"Younossi","year":"2019","journal-title":"J Hepatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41575-019-0144-8","article-title":"Past, present and future perspectives in nonalcoholic fatty liver disease.","volume":"16","author":"Sanyal","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases.","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1111\/liv.14828","article-title":"Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population.","volume":"41","author":"Ciardullo","year":"2021","journal-title":"Liver Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.","volume":"73","author":"Eslam","year":"2020","journal-title":"J Hepatol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100231","article-title":"NAFLD and MAFLD as emerging causes of HCC: a populational study.","volume":"3","author":"Myers","year":"2021","journal-title":"JHEP Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1002\/jcsm.12039","article-title":"Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis.","volume":"7","author":"Montano-Loza","year":"2016","journal-title":"J Cachexia Sarcopenia Muscle."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.dld.2019.05.034","article-title":"Clinical relevance of skeletal muscle abnormalities in patients with cirrhosis.","volume":"51","author":"Ebadi","year":"2019","journal-title":"Dig Liver Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1002\/hep.26716","article-title":"Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean sarcopenic obesity study.","volume":"59","author":"Hong","year":"2014","journal-title":"Hepatology."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1002\/hep.29420","article-title":"Sarcopenia in hiding: the risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis.","volume":"66","author":"Bhanji","year":"2017","journal-title":"Hepatology."},{"key":"B11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/lt.25346","article-title":"Differing impact of sarcopenia and frailty in nonalcoholic steatohepatitis and alcoholic liver disease.","volume":"25","author":"Bhanji","year":"2019","journal-title":"Liver Transplant."},{"key":"B12","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jhep.2016.08.019","article-title":"Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis.","volume":"66","author":"Koo","year":"2017","journal-title":"J Hepatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/apt.13889","article-title":"Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease.","volume":"45","author":"Petta","year":"2017","journal-title":"Aliment Pharmacol Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.clnu.2019.04.023","article-title":"Low muscle mass and low muscle strength associate with nonalcoholic fatty liver disease.","volume":"39","author":"Gan","year":"2020","journal-title":"Clin Nutr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1042\/cs20180421","article-title":"Emerging awareness on the importance of skeletal muscle in liver diseases: time to dig deeper into mechanisms!","volume":"133","author":"Nachit","year":"2019","journal-title":"Clin Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1002\/jcsm.12646","article-title":"Myosteatosis rather than sarcopenia associates with non-alcoholic steatohepatitis in non-alcoholic fatty liver disease preclinical models.","volume":"12","author":"Nachit","year":"2021","journal-title":"J Cachexia Sarcopenia Muscle."},{"key":"B17","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jhep.2021.02.037","article-title":"Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.","volume":"75","author":"Nachit","year":"2021","journal-title":"J Hepatol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1111\/jgh.12227","article-title":"Severity of non-alcoholic steatohepatitis is associated with substitution of adipose tissue in skeletal muscle.","volume":"28","author":"Kitajima","year":"2013","journal-title":"J Gastroenterol Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/liv.14253","article-title":"Relationship between nonalcoholic fatty liver disease and muscle quality as well as quantity evaluated by computed tomography.","volume":"40","author":"Tanaka","year":"2020","journal-title":"Liver Int."},{"key":"B20","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/hep.26908","article-title":"Presence of sarcopenia (muscle wasting) in patients with nonalcoholic steatohepatitis.","volume":"60","author":"Issa","year":"2014","journal-title":"Hepatology."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79718-9","article-title":"Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients.","volume":"11","author":"Lanthier","year":"2021","journal-title":"Sci Rep."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100323","article-title":"A dynamic association between myosteatosis and liver stiffness: results from a prospective interventional study in obese patients.","volume":"3","author":"Nachit","year":"2021","journal-title":"JHEP Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/978-1-4615-7166-7_6","article-title":"Ammonia metabolism.","volume":"27","author":"Bessman","year":"1964","journal-title":"Rev Neuropsiquiatr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1177\/0148607187011006569","article-title":"Interorgan ammonia metabolism in health and disease: a surgeon\u2019s view.","volume":"11","author":"Souba","year":"1987","journal-title":"J Parenter Enter Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1053\/jhep.2002.36497","article-title":"Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS.","volume":"36","author":"Olde Damink","year":"2002","journal-title":"Hepatology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0197-0186(02)00040-2","article-title":"Interorgan ammonia metabolism in liver failure.","volume":"41","author":"Olde Damink","year":"2002","journal-title":"Neurochem Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11011-008-9124-3","article-title":"Gut ammonia production and its modulation.","volume":"24","author":"Romero-G\u00f3mez","year":"2009","journal-title":"Metab Brain Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"40S","DOI":"10.1177\/014860719001400402","article-title":"Glutamine metabolism and its physiologic importance.","volume":"14","author":"Smith","year":"1990","journal-title":"J Parenter Enter Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S0899-9007(02)00739-6","article-title":"Hepatic glutamine metabolism.","volume":"18","author":"Watford","year":"2002","journal-title":"Nutrition."},{"key":"B30","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1201\/9781315373164","author":"Blachier","year":"2017","journal-title":"Glutamine and Intestinal Physiology and Pathology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"9516","DOI":"10.1074\/jbc.M109.092429","article-title":"Glutamine synthetase in muscle is required for glutamine production during fasting and extrahepatic ammonia detoxification.","volume":"285","author":"He","year":"2010","journal-title":"J Biol Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.jhep.2005.11.048","article-title":"Direct molecular and spectroscopic evidence for increased ammonia removal capacity of skeletal muscle in acute liver failure.","volume":"44","author":"Chatauret","year":"2006","journal-title":"J Hepatol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF02833598","article-title":"Ammonia: key factor in the pathogenesis of hepatic encephalopathy.","volume":"6","author":"Butterworth","year":"1987","journal-title":"Neurochem Pathol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s11011-008-9113-6","article-title":"Signaling factors in the mechanism of ammonia neurotoxicity.","volume":"24","author":"Norenberg","year":"2009","journal-title":"Metab Brain Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1007\/s11064-016-2014-x","article-title":"Neurotoxicity of ammonia.","volume":"42","author":"Oja","year":"2017","journal-title":"Neurochem Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.jhep.2016.06.004","article-title":"Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of L-leucine in cirrhosis.","volume":"65","author":"Davuluri","year":"2016","journal-title":"J Hepatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7341","DOI":"10.1113\/JP272796","article-title":"Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress.","volume":"594","author":"Davuluri","year":"2016","journal-title":"J Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1002\/hep.29107","article-title":"Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis.","volume":"65","author":"Kumar","year":"2017","journal-title":"Hepatology."},{"key":"B39","doi-asserted-by":"publisher","first-page":"18162","DOI":"10.1073\/pnas.1317049110","article-title":"Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-\u03baB-mediated mechanism.","volume":"110","author":"Qiu","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B40","doi-asserted-by":"publisher","first-page":"G163","DOI":"10.1152\/ajpgi.00322.2015","article-title":"Hyperammonemia results in reduced muscle function independent of muscle mass.","volume":"310","author":"McDaniel","year":"2016","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.jhep.2018.06.023","article-title":"Urea cycle dysregulation in non-alcoholic fatty liver disease.","volume":"69","author":"De Chiara","year":"2018","journal-title":"J Hepatol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1023\/A:1021934607762","article-title":"Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy.","volume":"17","author":"Kircheis","year":"2002","journal-title":"Metab Brain Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s40265-018-1023-2","article-title":"Pharmacokinetic and pharmacodynamic properties of l-ornithine l-aspartate (LOLA) in hepatic encephalopathy.","volume":"79","author":"Kircheis","year":"2019","journal-title":"Drugs."},{"key":"B44","first-page":"1","article-title":"Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels.","volume":"283","author":"Gebhardt","year":"1997","journal-title":"J Pharmacol Exp Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1152\/japplphysiol.00016.2010","article-title":"Rapid in vivo whole body composition of rats using cone beam \u03bcCT.","volume":"109","author":"Granton","year":"2010","journal-title":"J Appl Physiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41374-019-0315-9","article-title":"Automated computerized image analysis for the user-independent evaluation of disease severity in preclinical models of NAFLD\/NASH.","volume":"100","author":"De Rudder","year":"2020","journal-title":"Lab Investig."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1002\/hep.25889","article-title":"Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients.","volume":"56","author":"Bedossa","year":"2012","journal-title":"Hepatology."},{"key":"B48","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1172\/JCI8814","article-title":"CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis Find the latest version : CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis.","volume":"105","author":"Leclercq","year":"2000","journal-title":"J Clin Invest."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12070625","article-title":"Fetuin-A in activated liver macrophages is a key feature of non-alcoholic steatohepatitis.","volume":"12","author":"Etienne","year":"2022","journal-title":"Metabolites."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100387","article-title":"Bile acids contribute to the development of non-alcoholic steatohepatitis in mice.","volume":"4","author":"Gillard","year":"2022","journal-title":"JHEP Rep."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/nu14132707","article-title":"Enterohepatic takeda G-protein coupled receptor 5 agonism in metabolic dysfunction-associated fatty liver disease and related glucose dysmetabolism.","volume":"14","author":"Gillard","year":"2022","journal-title":"Nutrients."},{"key":"B52","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1111\/liv.14719","article-title":"Muscle alterations are independently associated with significant fibrosis in patients with nonalcoholic fatty liver disease.","volume":"41","author":"Hsieh","year":"2021","journal-title":"Liver Int."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.01.020","article-title":"Myosteatosis, but not sarcopenia, predisposes NAFLD subjects to early steatohepatitis and fibrosis progression.","author":"Hsieh","year":"2022","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.1007\/s10620-016-4285-0","article-title":"Diet-induced nonalcoholic fatty liver disease is associated with sarcopenia and decreased serum insulin-like growth factor-1.","volume":"61","author":"Cabrera","year":"2016","journal-title":"Dig Dis Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s11011-016-9938-3","article-title":"Ammonia toxicity: from head to toe?","volume":"32","author":"Dasarathy","year":"2017","journal-title":"Metab Brain Dis."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.jhep.2016.07.040","article-title":"Sarcopenia from mechanism to diagnosis and treatment in liver disease.","volume":"65","author":"Dasarathy","year":"2016","journal-title":"J Hepatol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3350\/cmh.2019.0015","article-title":"Sarcopenia: ammonia metabolism and hepatic encephalopathy.","volume":"25","author":"Jindal","year":"2019","journal-title":"Clin Mol Hepatol."},{"key":"B58","first-page":"308","article-title":"Blood ammonia concentration in mice: normal reference values and changes during growth.","volume":"40","author":"Koizumi","year":"1990","journal-title":"Lab Anim Sci."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102516","article-title":"Spatio-temporal multiscale analysis of western diet-fed mice reveals a translationally relevant sequence of events during NAFLD progression.","volume":"10","author":"Ghallab","year":"2021","journal-title":"Cells."},{"key":"B60","doi-asserted-by":"publisher","first-page":"G174","DOI":"10.1152\/AJPGI.00041.2019","article-title":"Comparison of murine steatohepatitis models identifies a dietary intervention with robust fibrosis, ductular reaction, and rapid progression to cirrhosis and cancer.","volume":"318","author":"Wei","year":"2020","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1002\/hep.30890","article-title":"Ammonia scavenging prevents progression of fibrosis in experimental nonalcoholic fatty liver disease.","volume":"71","author":"De Chiara","year":"2020","journal-title":"Hepatology."},{"key":"B62","doi-asserted-by":"publisher","first-page":"G295","DOI":"10.1152\/ajpgi.00036.2014","article-title":"Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function.","volume":"307","author":"Thomsen","year":"2014","journal-title":"Am J Physiol Liver Physiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1111\/liv.14205","article-title":"Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion.","volume":"39","author":"Eriksen","year":"2019","journal-title":"Liver Int."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-06614-9","article-title":"Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation.","volume":"12","author":"Gallego-Dur\u00e1n","year":"2022","journal-title":"Sci Rep."},{"key":"B65","doi-asserted-by":"publisher","first-page":"K86","DOI":"10.1016\/0014-5793(80)80573-4","article-title":"Glutamine metabolism in the rat.","volume":"117","author":"Lund","year":"1980","journal-title":"FEBS Lett."},{"key":"B66","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1042\/bj2160523","article-title":"Glutamine synthetase activity of muscle in acidosis.","volume":"216","author":"King","year":"1983","journal-title":"Biochem J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/0026-0495(76)90075-5","article-title":"Muscle nitrogen metabolism in chronic hepatic insufficiency.","volume":"25","author":"Ganda","year":"1976","journal-title":"Metabolism."},{"key":"B68","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1172\/JCI109322","article-title":"The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.","volume":"63","author":"Lockwood","year":"1979","journal-title":"J Clin Invest."},{"key":"B69","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.1365-2362.1982.tb02222.x","article-title":"Ammonia uptake by skeletal muscle in the hyperammonaemic rat.","volume":"12","author":"Hod","year":"1982","journal-title":"Eur J Clin Invest."},{"key":"B70","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.jhep.2009.11.019","article-title":"Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice.","volume":"52","author":"Navarro-Alvarez","year":"2010","journal-title":"J Hepatol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"4718","DOI":"10.1007\/s12035-018-1389-x","article-title":"Resveratrol restores neuronal tight junction proteins through correction of ammonia and inflammation in CCL4-induced cirrhotic mice.","volume":"56","author":"Vairappan","year":"2019","journal-title":"Mol Neurobiol."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-63139-9","article-title":"Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice.","volume":"10","author":"Chen","year":"2020","journal-title":"Sci Rep."},{"key":"B73","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11011-011-9269-3","article-title":"Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.","volume":"27","author":"Felipo","year":"2012","journal-title":"Metab Brain Dis."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jcm10040673","article-title":"Cognitive dysfunction in non-alcoholic fatty liver disease\u2014current knowledge, mechanisms and perspectives.","volume":"10","author":"Kj\u00e6rgaard","year":"2021","journal-title":"J Clin Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1136\/gutjnl-2017-313884","article-title":"Non-Alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.","volume":"66","author":"Adams","year":"2017","journal-title":"Gut."},{"key":"B76","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s11154-019-09537-5","article-title":"Microbiota impacts on chronic inflammation and metabolic syndrome - related cognitive dysfunction.","volume":"20","author":"Arnoriaga-Rodr\u00edguez","year":"2019","journal-title":"Rev Endocr Metab Disord."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1053\/j.gastro.2009.02.050","article-title":"Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study.","volume":"136","author":"Acharya","year":"2009","journal-title":"Gastroenterology."},{"key":"B78","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1111\/hepr.12235","article-title":"Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled trial.","volume":"44","author":"Alvares-da-Silva","year":"2014","journal-title":"Hepatol Res."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.808497","article-title":"Ammonia scavenger restores liver and muscle injury in a mouse model of non-alcoholic steatohepatitis with sarcopenic obesity.","volume":"9","author":"Wang","year":"2022","journal-title":"Front Nutr."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1111\/liv.14911","article-title":"2021 ISHEN guidelines on animal models of hepatic encephalopathy.","volume":"41","author":"DeMorrow","year":"2021","journal-title":"Liver Int."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1007\/s00018-005-5089-0","article-title":"The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation.","volume":"62","author":"Shawcross","year":"2005","journal-title":"Cell Mol Life Sci."},{"key":"B82","doi-asserted-by":"publisher","first-page":"G9","DOI":"10.1152\/ajpgi.00008.2012","article-title":"Liver cholesterol: is it playing possum in NASH?","volume":"303","author":"Farrell","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jhep.2013.02.024","article-title":"Pharmacological cholesterol lowering reverses fibrotic NASH in obese, diabetic mice with metabolic syndrome.","volume":"59","author":"Van Rooyen","year":"2013","journal-title":"J Hepatol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1016\/j.cmet.2021.09.001","article-title":"Cholesterol-induced toxicity: an integrated view of the role of cholesterol in multiple diseases.","volume":"33","author":"Song","year":"2021","journal-title":"Cell Metab."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.3945\/jn.115.218982","article-title":"Citrulline and nonessential amino acids prevent fructose-induced nonalcoholic fatty liver disease in rats1-3.","volume":"145","author":"Jegatheesan","year":"2015","journal-title":"J Nutr."},{"key":"B86","doi-asserted-by":"publisher","first-page":"4941","DOI":"10.1039\/d1fo03403k","article-title":"l-Methionine supplementation attenuates high-fat fructose diet-induced non-alcoholic steatohepatitis by modulating lipid metabolism, fibrosis, and inflammation in rats.","volume":"13","author":"Navik","year":"2022","journal-title":"Food Funct."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173914","article-title":"A morphological method for ammonia detection in liver.","volume":"12","author":"Guti\u00e9rrez-De-Juan","year":"2017","journal-title":"PLoS One."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1051157\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T05:40:09Z","timestamp":1668577209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1051157\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,16]]},"references-count":87,"alternative-id":["10.3389\/fnut.2022.1051157"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.1051157","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,16]]},"article-number":"1051157"}}