{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T18:33:47Z","timestamp":1794508427020,"version":"4.9.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Spitfire Pharma Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Body weight loss of\u2009\u2265\u200910% improves the metabolic derangements and liver disease in the majority of non-alcoholic steatohepatitis (NASH) patients, suggesting metabolic modulators may be effective in controlling disease. The pharmacodynamics of ALT-801, a GLP-1\/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-\u03b1\/\u03b4, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH). Male C57BL\/6J mice were fed Amylin Liver NASH (AMLN) diet for 32\u00a0weeks. Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12\u00a0weeks while maintained on the AMLN diet. Study endpoints included body and liver weight, liver and plasma total cholesterol and triglycerides, plasma aminotransferases, histological analysis of liver steatosis, inflammation (galectin-3) and fibrosis (collagen type 1 alpha 1), and evaluation of individual animal changes in composite Non-alcoholic Fatty Liver Disease Activity Score (NAS), and fibrosis stage. ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides\/total cholesterol in conjunction with improved liver steatosis, with greater reductions (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) compared to semaglutide and elafibranor. ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls. This study provides evidence for a potential role for ALT-801 in the therapeutic treatment of NASH.<\/jats:p>","DOI":"10.1038\/s41598-022-10577-2","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T10:02:49Z","timestamp":1650708169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis"],"prefix":"10.1038","volume":"12","author":[{"given":"John J.","family":"Nestor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Parkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Suschak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Scott","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"10577_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/MEG.0000000000001279","volume":"31","author":"S Softic","year":"2019","unstructured":"Softic, S. & Kahn, C. R. Fatty liver disease: Is it nonalcoholic fatty liver disease or obesity-associated fatty liver disease?. Eur. J. Gastroenterol. Hepatol. 31, 143. https:\/\/doi.org\/10.1097\/MEG.0000000000001279 (2019).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"10577_CR2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312","author":"M Eslam","year":"2020","unstructured":"Eslam, M., Sanyal, A. J., George, J., International Consensus, P. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology https:\/\/doi.org\/10.1053\/j.gastro.2019.11.312 (2020).","journal-title":"Gastroenterology"},{"key":"10577_CR3","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1056\/NEJMc1710026","volume":"377","author":"A Afshin","year":"2017","unstructured":"Afshin, A., Reitsma, M. B. & Murray, C. J. L. Health effects of overweight and obesity in 195 countries. N. Engl. J. Med. 377, 1496\u20131497. https:\/\/doi.org\/10.1056\/NEJMc1710026 (2017).","journal-title":"N. Engl. J. Med."},{"key":"10577_CR4","first-page":"64","volume":"36","author":"LM Glass","year":"2019","unstructured":"Glass, L. M., Hunt, C. M., Fuchs, M. & Su, G. L. Comorbidities and nonalcoholic fatty liver disease: The chicken, the egg, or both?. Fed. Pract. 36, 64\u201371 (2019).","journal-title":"Fed. Pract."},{"key":"10577_CR5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1007\/s00535-017-1415-1","volume":"53","author":"Y Sumida","year":"2018","unstructured":"Sumida, Y. & Yoneda, M. Current and future pharmacological therapies for NAFLD\/NASH. J. Gastroenterol. 53, 362\u2013376. https:\/\/doi.org\/10.1007\/s00535-017-1415-1 (2018).","journal-title":"J. Gastroenterol."},{"key":"10577_CR6","doi-asserted-by":"publisher","first-page":"R211","DOI":"10.1530\/EJE-19-0566","volume":"181","author":"MA Nauck","year":"2019","unstructured":"Nauck, M. A. & Meier, J. J. Management of endocrine disease: Are all GLP-1 agonists equal in the treatment of type 2 diabetes?. Eur. J. Endocrinol. 181, R211\u2013R234. https:\/\/doi.org\/10.1530\/EJE-19-0566 (2019).","journal-title":"Eur. J. Endocrinol."},{"key":"10577_CR7","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMoa2032183","volume":"384","author":"JPH Wilding","year":"2021","unstructured":"Wilding, J. P. H. et al. Once-weekly semaglutide in adults with overweight or obesity. N. Engl. J. Med. 384, 989. https:\/\/doi.org\/10.1056\/NEJMoa2032183 (2021).","journal-title":"N. Engl. J. Med."},{"key":"10577_CR8","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1056\/NEJMoa2107519","volume":"385","author":"JP Frias","year":"2021","unstructured":"Frias, J. P. et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N. Engl. J. Med. 385, 503\u2013515. https:\/\/doi.org\/10.1056\/NEJMoa2107519 (2021).","journal-title":"N. Engl. J. Med."},{"key":"10577_CR9","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","volume":"149","author":"E Vilar-Gomez","year":"2015","unstructured":"Vilar-Gomez, E. et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic Steatohepatitis. Gastroenterology 149, 367-378.e365. https:\/\/doi.org\/10.1053\/j.gastro.2015.04.005 (2015) (quiz e314\u2013365).","journal-title":"Gastroenterology"},{"key":"10577_CR10","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.gastrohep.2017.07.006","volume":"41","author":"J Ampuero","year":"2018","unstructured":"Ampuero, J., Sanchez-Torrijos, Y., Aguilera, V., Bellido, F. & Romero-Gomez, M. New therapeutic perspectives in non-alcoholic steatohepatitis. Gastroenterol. Hepatol. 41, 128\u2013142. https:\/\/doi.org\/10.1016\/j.gastrohep.2017.07.006 (2018).","journal-title":"Gastroenterol. Hepatol."},{"key":"10577_CR11","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1053\/j.gastro.2020.06.006","volume":"159","author":"G Lassailly","year":"2020","unstructured":"Lassailly, G. et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology 159, 1290-1301.e1295 (2020).","journal-title":"Gastroenterology"},{"key":"10577_CR12","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.2337\/db09-0278","volume":"58","author":"A Pocai","year":"2009","unstructured":"Pocai, A. et al. Glucagon-like peptide 1\/glucagon receptor dual agonism reverses obesity in mice. Diabetes 58, 2258\u20132266. https:\/\/doi.org\/10.2337\/db09-0278 (2009).","journal-title":"Diabetes"},{"key":"10577_CR13","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nchembio.209","volume":"5","author":"JW Day","year":"2009","unstructured":"Day, J. W. et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat. Chem. Biol. 5, 749\u2013757. https:\/\/doi.org\/10.1038\/nchembio.209 (2009).","journal-title":"Nat. Chem. Biol."},{"key":"10577_CR14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2174\/1871525716666180118152158","volume":"16","author":"V Patel","year":"2018","unstructured":"Patel, V. et al. Coagonist of GLP-1 and glucagon receptor ameliorates development of non-alcoholic fatty liver disease. Cardiovasc. Hematol. Agents Med. Chem. 16, 35\u201343. https:\/\/doi.org\/10.2174\/1871525716666180118152158 (2018).","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"10577_CR15","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/j.ejmech.2017.07.046","volume":"138","author":"J Zhou","year":"2017","unstructured":"Zhou, J. et al. A novel glucagon-like peptide-1\/glucagon receptor dual agonist exhibits weight-lowering and diabetes-protective effects. Eur. J. Med. Chem. 138, 1158\u20131169. https:\/\/doi.org\/10.1016\/j.ejmech.2017.07.046 (2017).","journal-title":"Eur. J. Med. Chem."},{"key":"10577_CR16","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1111\/dom.13212","volume":"20","author":"R Elvert","year":"2018","unstructured":"Elvert, R. et al. Running on mixed fuel-dual agonistic approach of GLP-1 and GCG receptors leads to beneficial impact on body weight and blood glucose control: A comparative study between mice and non-human primates. Diabetes Obes. Metab. 20, 1836\u20131851. https:\/\/doi.org\/10.1111\/dom.13212 (2018).","journal-title":"Diabetes Obes. Metab."},{"key":"10577_CR17","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/dom.13494","volume":"21","author":"J Tillner","year":"2019","unstructured":"Tillner, J. et al. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. Diabetes Obes. Metab. 21, 120\u2013128. https:\/\/doi.org\/10.1111\/dom.13494 (2019).","journal-title":"Diabetes Obes. Metab."},{"key":"10577_CR18","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/bip.22072","volume":"98","author":"JW Day","year":"2012","unstructured":"Day, J. W. et al. Optimization of co-agonism at GLP-1 and glucagon receptors to safely maximize weight reduction in DIO-rodents. Biopolymers 98, 443\u2013450. https:\/\/doi.org\/10.1002\/bip.22072 (2012).","journal-title":"Biopolymers"},{"key":"10577_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/pep2.24225","author":"JJ Nestor","year":"2021","unstructured":"Nestor, J. J. & Wang, W. Surfactant-modified parathyroid hormone fragments with high potency and prolonged action: Structure-informed design using glycolipid surfactant conjugation. Pept. Sci. https:\/\/doi.org\/10.1002\/pep2.24225 (2021).","journal-title":"Pept. Sci."},{"key":"10577_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/pep2.24221","author":"JJ Nestor","year":"2021","unstructured":"Nestor, J. J., Zhang, X., Jaw-Tsai, S., Parkes, D. G. & Becker, C. K. Design and characterization of a surfactant-conjugated, long-acting, balanced GLP-1\/glucagon receptor dual agonist. Pept. Sci. https:\/\/doi.org\/10.1002\/pep2.24221 (2021).","journal-title":"Pept. Sci."},{"key":"10577_CR21","unstructured":"Nestor, J. J., Jr., Zhang, X., Perlman, A., Parkes, D. G. & Jaw-Tsai, S. In Long-Acting GLP-1\/Glucagon Dual Agonist SP-1373 Shows Superior Body and Liver Weight Loss in DIO Rodent Models Relevant to Diabetes and NASH (Spitfire Pharma, Inc., 77th American Diabetes Association Scientific Sessions, 2017)."},{"key":"10577_CR22","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1016\/j.drudis.2017.06.007","volume":"22","author":"HH Hansen","year":"2017","unstructured":"Hansen, H. H. et al. Mouse models of nonalcoholic steatohepatitis in preclinical drug development. Drug Discov. Today 22, 1707\u20131718 (2017).","journal-title":"Drug Discov. Today"},{"key":"10577_CR23","unstructured":"Laboratory, J. Body weight information for C57BL\/6J (000664), https:\/\/www.jax.org\/jax-mice-and-services\/strain-data-sheet-pages\/body-weight-chart-000664 (2020)."},{"key":"10577_CR24","doi-asserted-by":"publisher","first-page":"4904","DOI":"10.3748\/wjg.v25.i33.4904","volume":"25","author":"ML Boland","year":"2019","unstructured":"Boland, M. L. et al. Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source. World J. Gastroenterol. 25, 4904 (2019).","journal-title":"World J. Gastroenterol."},{"key":"10577_CR25","doi-asserted-by":"publisher","first-page":"2923","DOI":"10.2337\/dc12-2012","volume":"36","author":"B Cariou","year":"2013","unstructured":"Cariou, B. et al. Dual peroxisome proliferator-activated receptor \u03b1\/\u03b4 agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care 36, 2923\u20132930 (2013).","journal-title":"Diabetes Care"},{"key":"10577_CR26","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.2337\/dc11-0093","volume":"34","author":"B Cariou","year":"2011","unstructured":"Cariou, B., Za\u00efr, Y., Staels, B. & Bruckert, E. Effects of the new dual PPAR\u03b1\/\u03b4 agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism. Diabetes Care 34, 2008\u20132014 (2011).","journal-title":"Diabetes Care"},{"key":"10577_CR27","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1111\/apt.16608","volume":"54","author":"A Flint","year":"2021","unstructured":"Flint, A. et al. Randomised clinical trial: Semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol. Ther. 54, 1150\u20131161. https:\/\/doi.org\/10.1111\/apt.16608 (2021).","journal-title":"Aliment Pharmacol. Ther."},{"key":"10577_CR28","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1002\/hep.26461","volume":"58","author":"B Staels","year":"2013","unstructured":"Staels, B. et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha\/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis. Hepatology 58, 1941\u20131952. https:\/\/doi.org\/10.1002\/hep.26461 (2013).","journal-title":"Hepatology"},{"key":"10577_CR29","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1053\/j.gastro.2016.01.038","volume":"150","author":"V Ratziu","year":"2016","unstructured":"Ratziu, V. et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-\u03b1 and -\u03b4, induces resolution of nonalcoholic Steatohepatitis without fibrosis worsening. Gastroenterology 150, 1147-1159.e1145. https:\/\/doi.org\/10.1053\/j.gastro.2016.01.038 (2016).","journal-title":"Gastroenterology"},{"key":"10577_CR30","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/apt.15316","volume":"50","author":"P Newsome","year":"2019","unstructured":"Newsome, P. et al. Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and\/or obesity. Aliment Pharmacol. Ther. 50, 193\u2013203. https:\/\/doi.org\/10.1111\/apt.15316 (2019).","journal-title":"Aliment Pharmacol. Ther."},{"key":"10577_CR31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/hep.23276","volume":"51","author":"K Promrat","year":"2010","unstructured":"Promrat, K. et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51, 121\u2013129 (2010).","journal-title":"Hepatology"},{"key":"10577_CR32","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1007\/s10620-014-3380-3","volume":"60","author":"LM Glass","year":"2015","unstructured":"Glass, L. M. et al. Total body weight loss of\u2265 10% is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig. Dis. Sci. 60, 1024\u20131030 (2015).","journal-title":"Dig. Dis. Sci."},{"key":"10577_CR33","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1002\/hep.28392","volume":"63","author":"G Marchesini","year":"2016","unstructured":"Marchesini, G., Petta, S. & Dalle Grave, R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology 63, 2032\u20132043 (2016).","journal-title":"Hepatology"},{"key":"10577_CR34","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1210\/en.2013-1934","volume":"155","author":"C Pyke","year":"2014","unstructured":"Pyke, C. et al. GLP-1 receptor localization in monkey and human tissue: Novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 155, 1280\u20131290. https:\/\/doi.org\/10.1210\/en.2013-1934 (2014).","journal-title":"Endocrinology"},{"key":"10577_CR35","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3389\/fendo.2019.00155","volume":"10","author":"LB Knudsen","year":"2019","unstructured":"Knudsen, L. B. & Lau, J. The discovery and development of liraglutide and semaglutide. Front. Endocrinol. (Lausanne) 10, 155. https:\/\/doi.org\/10.3389\/fendo.2019.00155 (2019).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"10577_CR36","unstructured":"Nestor, J. J., Jr. In Peptide-Based Drug Design ACS Professional Reference Book (eds. Taylor, M. D. & Amidon, G. L.) Ch. 19, 449\u2013471 (American Chemical Society, 1995)."},{"key":"10577_CR37","doi-asserted-by":"publisher","first-page":"4399","DOI":"10.2174\/092986709789712907","volume":"16","author":"JJ Nestor Jr","year":"2009","unstructured":"Nestor, J. J. Jr. The medicinal chemistry of peptides. Curr. Med. Chem. 16, 4399\u20134418. https:\/\/doi.org\/10.2174\/092986709789712907 (2009).","journal-title":"Curr. Med. Chem."},{"key":"10577_CR38","doi-asserted-by":"publisher","first-page":"7370","DOI":"10.1021\/acs.jmedchem.5b00726","volume":"58","author":"J Lau","year":"2015","unstructured":"Lau, J. et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J. Med. Chem. 58, 7370\u20137380. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00726 (2015).","journal-title":"J. Med. Chem."},{"key":"10577_CR39","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40591-016-0048-8","volume":"4","author":"MT Larsen","year":"2016","unstructured":"Larsen, M. T., Kuhlmann, M., Hvam, M. L. & Howard, K. A. Albumin-based drug delivery: Harnessing nature to cure disease. Mol. Cell Ther. 4, 3. https:\/\/doi.org\/10.1186\/s40591-016-0048-8 (2016).","journal-title":"Mol. Cell Ther."},{"key":"10577_CR40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/sj.jhh.1000537","volume":"12","author":"J Millar","year":"1998","unstructured":"Millar, J. Shortcomings in the trough to peak ratio as a guide to the dose interval for antihypertensive drugs. J. Hum. Hypertens. 12, 37\u201344 (1998).","journal-title":"J. Hum. Hypertens."},{"issue":"Suppl 1","key":"10577_CR41","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/dom.13162","volume":"20","author":"VR Aroda","year":"2018","unstructured":"Aroda, V. R. A review of GLP-1 receptor agonists: Evolution and advancement, through the lens of randomised controlled trials. Diabetes Obes. Metab. 20(Suppl 1), 22\u201333. https:\/\/doi.org\/10.1111\/dom.13162 (2018).","journal-title":"Diabetes Obes. Metab."},{"key":"10577_CR42","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1111\/dom.12735","volume":"18","author":"SJ Henderson","year":"2016","unstructured":"Henderson, S. J. et al. Robust anti-obesity and metabolic effects of a dual GLP-1\/glucagon receptor peptide agonist in rodents and non-human primates. Diabetes Obes. Metab. 18, 1176\u20131190. https:\/\/doi.org\/10.1111\/dom.12735 (2016).","journal-title":"Diabetes Obes. Metab."},{"key":"10577_CR43","unstructured":"Ribier, D., Tolborg, J. L., Hamprecht, D. W. & Thomas, L. Acylated glucagon analogue. United States patent US 10,336,802 B2 (2019)."},{"key":"10577_CR44","doi-asserted-by":"publisher","first-page":"673","DOI":"10.4254\/wjh.v8.i16.673","volume":"8","author":"MN Kristiansen","year":"2016","unstructured":"Kristiansen, M. N. et al. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy. World J. Hepatol. 8, 673\u2013684. https:\/\/doi.org\/10.4254\/wjh.v8.i16.673 (2016).","journal-title":"World J. Hepatol."},{"key":"10577_CR45","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3748\/wjg.v24.i2.179","volume":"24","author":"KS Tolbol","year":"2018","unstructured":"Tolbol, K. S. et al. Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis. World J. Gastroenterol. 24, 179\u2013194. https:\/\/doi.org\/10.3748\/wjg.v24.i2.179 (2018).","journal-title":"World J. Gastroenterol."},{"key":"10577_CR46","doi-asserted-by":"publisher","first-page":"G483","DOI":"10.1152\/ajpgi.00079.2013","volume":"305","author":"JR Clapper","year":"2013","unstructured":"Clapper, J. R. et al. Diet-induced mouse model of fatty liver disease and nonalcoholic steatohepatitis reflecting clinical disease progression and methods of assessment. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G483\u2013G495 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10577_CR47","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313\u20131321. https:\/\/doi.org\/10.1002\/hep.20701 (2005).","journal-title":"Hepatology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10577-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10577-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10577-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T01:49:40Z","timestamp":1669340980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10577-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,23]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["10577"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-10577-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,23]]},"assertion":[{"value":"10 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.J.N. is a consultant to Altimmune, Inc., holds a financial interest in the company, and holds patents on ALT-801 and the EuPort\u2122 technology used for peptide prolongation. D.P. is a consultant to Altimmune, Inc. M.F. is an employee of Gubra Aps, which conducted the trial. J.J.S. and M.S.H. are employees of Altimmune, Inc. and hold a financial interest in the company.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6666"}}