{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:42:36Z","timestamp":1777502556037,"version":"3.51.4"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We previously demonstrated that a common dietary protein component, wheat amylase trypsin inhibitors (ATI), stimulate intestinal macrophages and dendritic cells via toll like receptor 4. Activation of these intestinal myeloid cells elicits an inflammatory signal that is propagated to mesenteric lymph nodes, and that can facilitate extraintestinal inflammation. Mice were fed a well-defined high fat diet, with (HFD\/ATI) or without (HFD) nutritionally irrelevant amounts of ATI. Mice on HFD\/ATI developed only mild signs of intestinal inflammation and myeloid cell activation but displayed significantly higher serum triglycerides and transaminases compared to mice on HFD alone. Moreover, they showed increased visceral and liver fat, and a higher insulin resistance. ATI feeding promoted liver and adipose tissue inflammation, with M1-type macrophage polarization and infiltration, and enhanced liver fibrogenesis. Gluten, the major protein component of wheat, did not induce these pathologies. Therefore, wheat ATI ingestion in minute quantities comparable to human daily wheat consumption exacerbated features of the metabolic syndrome and non-alcoholic steatohepatitis, despite its irrelevant caloric value.<\/jats:p>","DOI":"10.1038\/s41598-019-53323-x","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T11:02:49Z","timestamp":1574679769000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dietary wheat amylase trypsin inhibitors promote features of murine non-alcoholic fatty liver disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Muhammad","family":"Ashfaq-Khan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misbah","family":"Aslam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Asif","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel Sascha","family":"Senkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih","family":"Yen-Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Strand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Ook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geethanjali","family":"Pickert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rn M.","family":"Schattenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlef","family":"Schuppan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"53323_CR1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/hep.29466","volume":"67","author":"C Estes","year":"2018","unstructured":"Estes, C., Razavi, H., Loomba, R., Younossi, Z. & Sanyal, A. J. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 67, 123\u2013133, https:\/\/doi.org\/10.1002\/hep.29466 (2018).","journal-title":"Hepatology"},{"key":"53323_CR2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi, Z. M. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64, 73\u201384, https:\/\/doi.org\/10.1002\/hep.28431 (2016).","journal-title":"Hepatology"},{"key":"53323_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/liv.13299","volume":"37","author":"S Bellentani","year":"2017","unstructured":"Bellentani, S. The epidemiology of non-alcoholic fatty liver disease. Liver International 37, 81\u201384, https:\/\/doi.org\/10.1111\/liv.13299 (2017).","journal-title":"Liver International"},{"key":"53323_CR4","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.beem.2016.06.006","volume":"30","author":"S Lallukka","year":"2016","unstructured":"Lallukka, S. & Yki-Jarvinen, H. Non-alcoholic fatty liver disease and risk of type 2 diabetes. Best practice & research. Clinical endocrinology & metabolism 30, 385\u2013395, https:\/\/doi.org\/10.1016\/j.beem.2016.06.006 (2016).","journal-title":"Best practice & research. Clinical endocrinology & metabolism"},{"key":"53323_CR5","doi-asserted-by":"publisher","first-page":"d3897","DOI":"10.1136\/bmj.d3897","volume":"343","author":"QM Anstee","year":"2011","unstructured":"Anstee, Q. M., McPherson, S. & Day, C. P. How big a problem is non-alcoholic fatty liver disease? BMJ 343, d3897, https:\/\/doi.org\/10.1136\/bmj.d3897 (2011).","journal-title":"BMJ"},{"key":"53323_CR6","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1136\/gutjnl-2017-313884","volume":"66","author":"LA Adams","year":"2017","unstructured":"Adams, L. A., Anstee, Q. M., Tilg, H. & Targher, G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66, 1138\u20131153, https:\/\/doi.org\/10.1136\/gutjnl-2017-313884 (2017).","journal-title":"Gut"},{"key":"53323_CR7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/nrgastro.2016.147","volume":"14","author":"H Tilg","year":"2017","unstructured":"Tilg, H., Moschen, A. R. & Roden, M. NAFLD and diabetes mellitus. Nature reviews. Gastroenterology & hepatology 14, 32\u201342, https:\/\/doi.org\/10.1038\/nrgastro.2016.147 (2017).","journal-title":"Gastroenterology & hepatology"},{"key":"53323_CR8","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/hep.29085","volume":"65","author":"PS Dulai","year":"2017","unstructured":"Dulai, P. S. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 65, 1557\u20131565, https:\/\/doi.org\/10.1002\/hep.29085 (2017).","journal-title":"Hepatology"},{"key":"53323_CR9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","volume":"149","author":"P Angulo","year":"2015","unstructured":"Angulo, P. et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 149, 389\u2013397 e310, https:\/\/doi.org\/10.1053\/j.gastro.2015.04.043 (2015).","journal-title":"Gastroenterology"},{"key":"53323_CR10","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jhep.2017.11.012","volume":"68","author":"D Schuppan","year":"2018","unstructured":"Schuppan, D., Surabattula, R. & Wang, X. Y. Determinants of fibrosis progression and regression in NASH. Journal of hepatology 68, 238\u2013250, https:\/\/doi.org\/10.1016\/j.jhep.2017.11.012 (2018).","journal-title":"Journal of hepatology"},{"key":"53323_CR11","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","volume":"10","author":"QM Anstee","year":"2013","unstructured":"Anstee, Q. M., Targher, G. & Day, C. P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nature reviews. Gastroenterology & hepatology 10, 330\u2013344, https:\/\/doi.org\/10.1038\/nrgastro.2013.41 (2013).","journal-title":"Gastroenterology & hepatology"},{"key":"53323_CR12","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1002\/hep.28356","volume":"63","author":"J Boursier","year":"2016","unstructured":"Boursier, J. et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63, 764\u2013775, https:\/\/doi.org\/10.1002\/hep.28356 (2016).","journal-title":"Hepatology"},{"key":"53323_CR13","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1146\/annurev-pathol-012615-044224","volume":"11","author":"T Hardy","year":"2016","unstructured":"Hardy, T., Oakley, F., Anstee, Q. M. & Day, C. P. Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease. Spectrum. Annual review of pathology 11, 451\u2013496, https:\/\/doi.org\/10.1146\/annurev-pathol-012615-044224 (2016).","journal-title":"Spectrum. Annual review of pathology"},{"key":"53323_CR14","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1055\/s-0036-1593880","volume":"36","author":"EM Quigley","year":"2016","unstructured":"Quigley, E. M., Abu-Shanab, A., Murphy, E. F., Stanton, C. & Monsour, H. P. Jr. The Metabolic Role of the Microbiome: Implications for NAFLD and the Metabolic Syndrome. Seminars in liver disease 36, 312\u2013316, https:\/\/doi.org\/10.1055\/s-0036-1593880 (2016).","journal-title":"Seminars in liver disease"},{"key":"53323_CR15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1172\/JCI88879","volume":"127","author":"DA Winer","year":"2017","unstructured":"Winer, D. A., Winer, S., Dranse, H. J. & Lam, T. K. Immunologic impact of the intestine in metabolic disease. J Clin Invest 127, 33\u201342, https:\/\/doi.org\/10.1172\/JCI88879 (2017).","journal-title":"J Clin Invest"},{"key":"53323_CR16","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1002\/hep.21060","volume":"43","author":"V Racanelli","year":"2006","unstructured":"Racanelli, V. & Rehermann, B. The liver as an immunological organ. Hepatology 43, S54\u201362, https:\/\/doi.org\/10.1002\/hep.21060 (2006).","journal-title":"Hepatology"},{"key":"53323_CR17","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.numecd.2012.02.007","volume":"22","author":"D Compare","year":"2012","unstructured":"Compare, D. et al. Gut\u2013liver axis: the impact of gut microbiota on non alcoholic fatty liver disease. Nutrition, metabolism, and cardiovascular diseases: NMCD 22, 471\u2013476, https:\/\/doi.org\/10.1016\/j.numecd.2012.02.007 (2012).","journal-title":"Nutrition, metabolism, and cardiovascular diseases: NMCD"},{"key":"53323_CR18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/00075198-200104000-00008","volume":"7","author":"K Sheth","year":"2001","unstructured":"Sheth, K. & Bankey, P. The liver as an immune organ. Current opinion in critical care 7, 99\u2013104 (2001).","journal-title":"Current opinion in critical care"},{"key":"53323_CR19","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.3748\/wjg.v13.i11.1732","volume":"13","author":"X Jin","year":"2007","unstructured":"Jin, X., Yu, C. H., Lv, G. C. & Li, Y. M. Increased intestinal permeability in pathogenesis and progress of nonalcoholic steatohepatitis in rats. World journal of gastroenterology: WJG 13, 1732\u20131736 (2007).","journal-title":"World journal of gastroenterology: WJG"},{"key":"53323_CR20","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1002\/hep.24611","volume":"54","author":"A Alisi","year":"2011","unstructured":"Alisi, A., Carsetti, R. & Nobili, V. Pathogen- or damage-associated molecular patterns during nonalcoholic fatty liver disease development. Hepatology 54, 1500\u20131502, https:\/\/doi.org\/10.1002\/hep.24611 (2011).","journal-title":"Hepatology"},{"key":"53323_CR21","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1097\/MPG.0b013e3181c7bdf1","volume":"50","author":"A Alisi","year":"2010","unstructured":"Alisi, A., Manco, M., Devito, R., Piemonte, F. & Nobili, V. Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children. Journal of pediatric gastroenterology and nutrition 50, 645\u2013649, https:\/\/doi.org\/10.1097\/MPG.0b013e3181c7bdf1 (2010).","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"key":"53323_CR22","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.cmet.2017.02.001","volume":"25","author":"F Leulier","year":"2017","unstructured":"Leulier, F. et al. Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health. Cell metabolism 25, 522\u2013534, https:\/\/doi.org\/10.1016\/j.cmet.2017.02.001 (2017).","journal-title":"Cell metabolism"},{"key":"53323_CR23","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1146\/annurev-nutr-071715-051118","volume":"36","author":"D Raubenheimer","year":"2016","unstructured":"Raubenheimer, D. & Simpson, S. J. Nutritional Ecology and Human Health. Annual review of nutrition 36, 603\u2013626, https:\/\/doi.org\/10.1146\/annurev-nutr-071715-051118 (2016).","journal-title":"Annual review of nutrition"},{"key":"53323_CR24","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1084\/jem.20102660","volume":"209","author":"Y Junker","year":"2012","unstructured":"Junker, Y. et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med 209, 2395\u20132408, https:\/\/doi.org\/10.1084\/jem.20102660 (2012).","journal-title":"J Exp Med"},{"key":"53323_CR25","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1053\/j.gastro.2016.12.006","volume":"152","author":"VF Zevallos","year":"2017","unstructured":"Zevallos, V. F. et al. Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells. Gastroenterology 152, 1100\u20131113 e1112, https:\/\/doi.org\/10.1053\/j.gastro.2016.12.006 (2017).","journal-title":"Gastroenterology"},{"key":"53323_CR26","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1007\/s00394-018-1681-6","volume":"58","author":"VF Zevallos","year":"2019","unstructured":"Zevallos, V. F. et al. Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway inflammation. European journal of nutrition 58, 1507\u20131514, https:\/\/doi.org\/10.1007\/s00394-018-1681-6 (2019).","journal-title":"European journal of nutrition"},{"key":"53323_CR27","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jaci.2018.02.041","volume":"143","author":"I Bellinghausen","year":"2019","unstructured":"Bellinghausen, I. et al. Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice. The Journal of allergy and clinical immunology 143, 201\u2013212 e204, https:\/\/doi.org\/10.1016\/j.jaci.2018.02.041 (2019).","journal-title":"The Journal of allergy and clinical immunology"},{"key":"53323_CR28","doi-asserted-by":"publisher","first-page":"584","DOI":"10.15537\/smj.2016.5.15042","volume":"37","author":"NA Abdul-Rahman","year":"2016","unstructured":"Abdul-Rahman, N. A., Azman, R. R. & Kumar, G. Adult female with acute renal failure and weight loss. Saudi medical journal 37, 584\u2013586, https:\/\/doi.org\/10.15537\/smj.2016.5.15042 (2016).","journal-title":"Saudi medical journal"},{"key":"53323_CR29","doi-asserted-by":"publisher","first-page":"e100562","DOI":"10.1371\/journal.pone.0100562","volume":"9","author":"DK Zaafar","year":"2014","unstructured":"Zaafar, D. K., Zaitone, S. A. & Moustafa, Y. M. Role of metformin in suppressing 1,2-dimethylhydrazine-induced colon cancer in diabetic and non-diabetic mice: effect on tumor angiogenesis and cell proliferation. PloS one 9, e100562, https:\/\/doi.org\/10.1371\/journal.pone.0100562 (2014).","journal-title":"PloS one"},{"key":"53323_CR30","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1590\/2359-3997000000169","volume":"60","author":"LC Antunes","year":"2016","unstructured":"Antunes, L. C., Elkfury, J. L., Jornada, M. N., Foletto, K. C. & Bertoluci, M. C. Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Archives of endocrinology and metabolism 60, 138\u2013142, https:\/\/doi.org\/10.1590\/2359-3997000000169 (2016).","journal-title":"Archives of endocrinology and metabolism"},{"key":"53323_CR31","doi-asserted-by":"publisher","first-page":"15090","DOI":"10.1074\/jbc.M600030200","volume":"281","author":"Y Popov","year":"2006","unstructured":"Popov, Y. et al. Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB. J Biol Chem 281, 15090\u201315098, https:\/\/doi.org\/10.1074\/jbc.M600030200 (2006).","journal-title":"J Biol Chem"},{"key":"53323_CR32","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"},{"key":"53323_CR33","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1089\/ars.2016.6953","volume":"28","author":"X Wang","year":"2018","unstructured":"Wang, X. et al. Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nonalcoholic Steatohepatitis and Liver Fibrosis. Antioxidants & redox signaling 28, 87\u2013109, https:\/\/doi.org\/10.1089\/ars.2016.6953 (2018).","journal-title":"Antioxidants & redox signaling"},{"key":"53323_CR34","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1194\/jlr.M500294-JLR200","volume":"46","author":"S Cinti","year":"2005","unstructured":"Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. Journal of lipid research 46, 2347\u20132355, https:\/\/doi.org\/10.1194\/jlr.M500294-JLR200 (2005).","journal-title":"Journal of lipid research"},{"key":"53323_CR35","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.2337\/db07-0767","volume":"56","author":"KJ Strissel","year":"2007","unstructured":"Strissel, K. J. et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56, 2910\u20132918, https:\/\/doi.org\/10.2337\/db07-0767 (2007).","journal-title":"Diabetes"},{"key":"53323_CR36","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1194\/jlr.M800019-JLR200","volume":"49","author":"I Murano","year":"2008","unstructured":"Murano, I. et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. Journal of lipid research 49, 1562\u20131568, https:\/\/doi.org\/10.1194\/jlr.M800019-JLR200 (2008).","journal-title":"Journal of lipid research"},{"key":"53323_CR37","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1053\/j.gastro.2014.12.049","volume":"148","author":"A Fasano","year":"2015","unstructured":"Fasano, A., Sapone, A., Zevallos, V. & Schuppan, D. Nonceliac gluten sensitivity. Gastroenterology 148, 1195\u20131204, https:\/\/doi.org\/10.1053\/j.gastro.2014.12.049 (2015).","journal-title":"Gastroenterology"},{"key":"53323_CR38","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.bpg.2015.04.002","volume":"29","author":"D Schuppan","year":"2015","unstructured":"Schuppan, D., Pickert, G., Ashfaq-Khan, M. & Zevallos, V. Non-celiac wheat sensitivity: differential diagnosis, triggers and implications. Best Pract Res Clin Gastroenterol 29, 469\u2013476, https:\/\/doi.org\/10.1016\/j.bpg.2015.04.002 (2015).","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"53323_CR39","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1053\/j.gastro.2015.01.044","volume":"148","author":"CP Kelly","year":"2015","unstructured":"Kelly, C. P., Bai, J. C., Liu, E. & Leffler, D. A. Advances in diagnosis and management of celiac disease. Gastroenterology 148, 1175\u20131186, https:\/\/doi.org\/10.1053\/j.gastro.2015.01.044 (2015).","journal-title":"Gastroenterology"},{"key":"53323_CR40","doi-asserted-by":"publisher","unstructured":"Catassi, C. et al. The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update. Nutrients 9, https:\/\/doi.org\/10.3390\/nu9111268 (2017)","DOI":"10.3390\/nu9111268"},{"key":"53323_CR41","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.cell.2013.01.041","volume":"152","author":"AM Johnson","year":"2013","unstructured":"Johnson, A. M. & Olefsky, J. M. The origins and drivers of insulin resistance. Cell 152, 673\u2013684, https:\/\/doi.org\/10.1016\/j.cell.2013.01.041 (2013).","journal-title":"Cell"},{"key":"53323_CR42","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.clinbiochem.2015.06.023","volume":"48","author":"IA Kirpich","year":"2015","unstructured":"Kirpich, I. A., Marsano, L. S. & McClain, C. J. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clin Biochem 48, 923\u2013930, https:\/\/doi.org\/10.1016\/j.clinbiochem.2015.06.023 (2015).","journal-title":"Clin Biochem"},{"key":"53323_CR43","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.2337\/db10-0224","volume":"59","author":"C Duval","year":"2010","unstructured":"Duval, C. et al. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL\/6 mice. Diabetes 59, 3181\u20133191, https:\/\/doi.org\/10.2337\/db10-0224 (2010).","journal-title":"Diabetes"},{"key":"53323_CR44","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1172\/JCI29881","volume":"117","author":"CN Lumeng","year":"2007","unstructured":"Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117, 175\u2013184, https:\/\/doi.org\/10.1172\/JCI29881 (2007).","journal-title":"J Clin Invest"},{"key":"53323_CR45","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1053\/j.gastro.2015.05.044","volume":"149","author":"J du Plessis","year":"2015","unstructured":"du Plessis, J. et al. Association of Adipose Tissue Inflammation With Histologic Severity of Nonalcoholic Fatty Liver Disease. Gastroenterology 149, 635\u2013648 e614, https:\/\/doi.org\/10.1053\/j.gastro.2015.05.044 (2015).","journal-title":"Gastroenterology"},{"key":"53323_CR46","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1016\/j.ajpath.2014.01.034","volume":"184","author":"JK Dowman","year":"2014","unstructured":"Dowman, J. K. et al. Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat\/fructose diet and sedentary lifestyle. The American journal of pathology 184, 1550\u20131561, https:\/\/doi.org\/10.1016\/j.ajpath.2014.01.034 (2014).","journal-title":"The American journal of pathology"},{"key":"53323_CR47","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.humpath.2011.07.007","volume":"43","author":"CD Guy","year":"2012","unstructured":"Guy, C. D. et al. Costaining for keratins 8\/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Human pathology 43, 790\u2013800, https:\/\/doi.org\/10.1016\/j.humpath.2011.07.007 (2012).","journal-title":"Human pathology"},{"key":"53323_CR48","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.jhep.2017.10.031","volume":"68","author":"PK Santhekadur","year":"2018","unstructured":"Santhekadur, P. K., Kumar, D. P. & Sanyal, A. J. Preclinical models of non-alcoholic fatty liver disease. Journal of hepatology 68, 230\u2013237, https:\/\/doi.org\/10.1016\/j.jhep.2017.10.031 (2018).","journal-title":"Journal of hepatology"},{"key":"53323_CR49","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1002\/hep.30333","volume":"69","author":"G Farrell","year":"2019","unstructured":"Farrell, G. & Schattenberg, J. M. Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis. 69, 2241\u20132257, https:\/\/doi.org\/10.1002\/hep.30333 (2019).","journal-title":"Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53323-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53323-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53323-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T16:23:18Z","timestamp":1671294198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53323-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,25]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["53323"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-53323-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,25]]},"assertion":[{"value":"28 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17463"}}