{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:35:29Z","timestamp":1789763729794,"version":"4.0.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1007\/s10620-020-06280-9","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T04:26:57Z","timestamp":1588652817000},"page":"1090-1096","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["G-Protein-Coupled Receptors 120 Agonist III Improves Hepatic Inflammation and ER Stress in Steatohepatitis"],"prefix":"10.1007","volume":"66","author":[{"given":"Xiaoyuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,5]]},"reference":[{"key":"6280_CR1","doi-asserted-by":"crossref","unstructured":"Santhekadur PK, Kumar DP, Sanyal AJ. Preclinical Models of Nonalcoholic Fatty Liver Disease. J Hepatol. 2018;68(2):230\u2013237.","DOI":"10.1016\/j.jhep.2017.10.031"},{"key":"6280_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S2468-1253(16)30011-5","volume":"1","author":"VW Wong","year":"2016","unstructured":"Wong VW, Chitturi S, Wong GL, et al. Pathogenesis and novel treatment options for non-alcoholic steatohepatitis. Lancet Gastroenterol Hepatol. 2016;1:56\u201367.","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"6280_CR3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/164_2016_46","volume":"236","author":"FM Gribble","year":"2017","unstructured":"Gribble FM, Diakogiannaki E, Reimann F. Gut hormone regulation and secretion via FFA1 and FFA4. Handb Exp Pharmacol. 2017;236:181\u2013203.","journal-title":"Handb Exp Pharmacol"},{"key":"6280_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/164_2016_60","volume":"236","author":"SV Hansen","year":"2017","unstructured":"Hansen SV, Ulven T. Pharmacological tool compounds for the free fatty acid receptor 4 (FFA4\/GPR120). Handb Exp Pharmacol. 2017;236:33\u201356.","journal-title":"Handb Exp Pharmacol"},{"key":"6280_CR5","doi-asserted-by":"publisher","first-page":"4987","DOI":"10.1096\/fj.13-235333","volume":"27","author":"X Li","year":"2013","unstructured":"Li X, Yu Y, Funk CD. Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4). Faseb J. 2013;27:4987\u20134997.","journal-title":"Faseb J"},{"key":"6280_CR6","doi-asserted-by":"crossref","unstructured":"Im DS. FFA4 (GPR120) as a fatty acid sensor involved in appetite control, insulin sensitivity and inflammation regulation. Mol Asp Med. 2018;64:92\u2013108.","DOI":"10.1016\/j.mam.2017.09.001"},{"key":"6280_CR7","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nm.3614","volume":"20","author":"DY Oh","year":"2014","unstructured":"Oh DY, Walenta E, Akiyama TE, et al. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat Med. 2014;20:942\u2013947.","journal-title":"Nat Med"},{"key":"6280_CR8","doi-asserted-by":"publisher","first-page":"4192","DOI":"10.7150\/thno.21400","volume":"7","author":"J Du","year":"2017","unstructured":"Du J, Zhang X, Han J, et al. Pro-inflammatory CXCR3 impairs mitochondrial function in experimental nonalcoholic steatohepatitis. Theranostics. 2017;7:4192\u20134203.","journal-title":"Theranostics"},{"key":"6280_CR9","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.jhep.2015.09.005","volume":"64","author":"X Zhang","year":"2016","unstructured":"Zhang X, Han J, Man K, et al. CXC chemokine receptor 3 promotes steatohepatitis in mice through mediating inflammatory cytokines, macrophages and autophagy. J Hepatol. 2016;64:160\u2013170.","journal-title":"J Hepatol"},{"key":"6280_CR10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jnutbio.2018.12.003","volume":"66","author":"RC Gaspar","year":"2019","unstructured":"Gaspar RC, Veiga CB, Bessi MP, et al. Unsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: a new anti-inflammatory approach. J Nutr Biochem. 2019;66:52\u201362.","journal-title":"J Nutr Biochem"},{"key":"6280_CR11","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1016\/j.bmcl.2018.06.047","volume":"28","author":"R Sheng","year":"2018","unstructured":"Sheng R, Yang L, Zhang Y, et al. Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design. Bioorg Med Chem Lett. 2018;28:2599\u20132604.","journal-title":"Bioorg Med Chem Lett"},{"key":"6280_CR12","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1002\/hep.24376","volume":"54","author":"AJ Sanyal","year":"2011","unstructured":"Sanyal AJ, Brunt EM, Kleiner DE, et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011;54:344\u2013353.","journal-title":"Hepatology"},{"key":"6280_CR13","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313\u20131321.","journal-title":"Hepatology"},{"key":"6280_CR14","doi-asserted-by":"crossref","unstructured":"Xu B, Jiang M, Chu Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J Hepatol. 2018;68(4):773\u2013782.","DOI":"10.1016\/j.jhep.2017.11.040"},{"key":"6280_CR15","first-page":"2890","volume":"10","author":"L Yu","year":"2018","unstructured":"Yu L, Zhang W, Huang C, et al. FoxO4 promotes myocardial ischemia-reperfusion injury: the role of oxidative stress-induced apoptosis. Am J Transl Res. 2018;10:2890\u20132900.","journal-title":"Am J Transl Res"},{"key":"6280_CR16","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/j.jhep.2014.07.006","volume":"61","author":"X Zhang","year":"2014","unstructured":"Zhang X, Shen J, Man K, et al. CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis. J Hepatol. 2014;61:1365\u20131375.","journal-title":"J Hepatol"},{"key":"6280_CR17","first-page":"149","volume":"6","author":"GC Farrell","year":"2012","unstructured":"Farrell GC, van Rooyen D, Gan L, et al. NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications. gut. Liver. 2012;6:149\u2013171.","journal-title":"Liver"},{"key":"6280_CR18","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/path.4829","volume":"241","author":"JK Lau","year":"2017","unstructured":"Lau JK, Zhang X, Yu J. Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances. J Pathol. 2017;241:36\u201344.","journal-title":"J Pathol"},{"key":"6280_CR19","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nature10798","volume":"483","author":"A Ichimura","year":"2012","unstructured":"Ichimura A, Hirasawa A, Poulain-Godefroy O, et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012;483:350\u2013354.","journal-title":"Nature"},{"key":"6280_CR20","first-page":"3769","volume":"17","author":"H Wang","year":"2018","unstructured":"Wang H, Zhang H, Huang B, et al. Mesenchymal stem cells reverse high-fat diet-induced nonalcoholic fatty liver disease through suppression of CD4\u2009+\u2009T lymphocytes in mice. Mol Med Rep. 2018;17:3769\u20133774.","journal-title":"Mol Med Rep"},{"key":"6280_CR21","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.dld.2009.01.004","volume":"41","author":"S Petta","year":"2009","unstructured":"Petta S, Muratore C, Craxi A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis. 2009;41:615\u2013625.","journal-title":"Dig Liver Dis"},{"key":"6280_CR22","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/S0168-8278(03)00376-3","volume":"39","author":"J George","year":"2003","unstructured":"George J, Pera N, Phung N, et al. Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis. J Hepatol. 2003;39:756\u2013764.","journal-title":"J Hepatol"},{"key":"6280_CR23","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ccr.2014.07.001","volume":"26","author":"H Nakagawa","year":"2014","unstructured":"Nakagawa H, Umemura A, Taniguchi K, et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 2014;26:331\u2013343.","journal-title":"Cancer Cell"},{"key":"6280_CR24","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1128\/MCB.26.8.3071-3084.2006","volume":"26","author":"P Hu","year":"2006","unstructured":"Hu P, Han Z, Couvillon AD, et al. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol. 2006;26:3071\u20133084.","journal-title":"Mol Cell Biol"},{"key":"6280_CR25","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nm1168","volume":"11","author":"A Hirasawa","year":"2005","unstructured":"Hirasawa A, Tsumaya K, Awaji T, et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med. 2005;11:90\u201394.","journal-title":"Nat Med"},{"key":"6280_CR26","first-page":"252","volume":"42","author":"JI Shin","year":"2019","unstructured":"Shin JI, Jeon YJ, Lee S, et al. G-protein-coupled receptor 120 mediates DHA-induced apoptosis by regulating IP3R, ROS and ER stress levels in cisplatin-resistant cancer cells. Mol Cells. 2019;42:252\u2013261.","journal-title":"Mol Cells"},{"key":"6280_CR27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.mad.2016.07.001","volume":"157","author":"P Bozaykut","year":"2016","unstructured":"Bozaykut P, Sahin A, Karademir B, et al. Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis. Mech Ageing Dev. 2016;157:17\u201329.","journal-title":"Mech Ageing Dev"},{"key":"6280_CR28","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12944-018-0659-y","volume":"17","author":"X Su","year":"2018","unstructured":"Su X, Peng DQ. New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of cardiovascular diseases. Lipids Health Dis. 2018;17:12.","journal-title":"Lipids Health Dis"},{"key":"6280_CR29","first-page":"729","volume":"5","author":"M Miyazaki","year":"2012","unstructured":"Miyazaki M, Kato M, Tanaka K, et al. Increased hepatic expression of dipeptidyl peptidase-4 in non-alcoholic fatty liver disease and its association with insulin resistance and glucose metabolism. Mol Med Rep. 2012;5:729\u2013733.","journal-title":"Mol Med Rep"},{"key":"6280_CR30","doi-asserted-by":"publisher","first-page":"E214","DOI":"10.1152\/ajpendo.00553.2014","volume":"309","author":"T Shinjo","year":"2015","unstructured":"Shinjo T, Nakatsu Y, Iwashita M, et al. DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-kappaB activation. Am J Physiol Endocrinol Metab. 2015;309:E214\u2013E223.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"6280_CR31","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1530\/JME-12-0039","volume":"49","author":"S Shimizu","year":"2012","unstructured":"Shimizu S, Hosooka T, Matsuda T, et al. DPP4 inhibitor vildagliptin preserves beta-cell mass through amelioration of endoplasmic reticulum stress in C\/EBPB transgenic mice. J Mol Endocrinol. 2012;49:125\u2013135.","journal-title":"J Mol Endocrinol"},{"key":"6280_CR32","doi-asserted-by":"publisher","first-page":"9220","DOI":"10.1128\/MCB.01453-06","volume":"26","author":"M Ogata","year":"2006","unstructured":"Ogata M, Hino S, Saito A, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26:9220\u20139231.","journal-title":"Mol Cell Biol"},{"key":"6280_CR33","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/1475-2840-12-158","volume":"12","author":"ZW Liu","year":"2013","unstructured":"Liu ZW, Zhu HT, Chen KL, et al. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy. Cardiovasc Diabetol. 2013;12:158.","journal-title":"Cardiovasc Diabetol"},{"key":"6280_CR34","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1038\/cdd.2012.74","volume":"19","author":"T Verfaillie","year":"2012","unstructured":"Verfaillie T, Rubio N, Garg AD, et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ. 2012;19:1880\u20131891.","journal-title":"Cell Death Differ"}],"container-title":["Digestive Diseases and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-020-06280-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10620-020-06280-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-020-06280-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:06:10Z","timestamp":1620173170000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10620-020-06280-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,5]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["6280"],"URL":"https:\/\/doi.org\/10.1007\/s10620-020-06280-9","relation":{},"ISSN":["0163-2116","1573-2568"],"issn-type":[{"value":"0163-2116","type":"print"},{"value":"1573-2568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,5]]},"assertion":[{"value":"2 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal experimental procedures were performed in accordance with guidelines approved by the Institutional Animal Care and Use Committee at the Xi\u2019an Jiaotong University.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}}]}}