{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:32:57Z","timestamp":1792006377145,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100015601","name":"Collaborative Innovationcenter of Food Safety and Quality Control in Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773064"],"award-info":[{"award-number":["81773064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272290"],"award-info":[{"award-number":["32272290"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972973"],"award-info":[{"award-number":["31972973"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018635","name":"Thousand Young Talents Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Defective insulin signalling and dysfunction of the endoplasmic reticulum (ER), driven by excessive lipid accumulation in the liver, is a characteristic feature in the pathogenesis of non\u2010alcoholic fatty liver disease (NAFLD). Thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      (TXA\n                      <jats:sub>2<\/jats:sub>\n                      ), an arachidonic acid metabolite, is significantly elevated in obesity and plays a crucial role in hepatic gluconeogenesis and adipose tissue macrophage polarization. However, the role of liver TXA\n                      <jats:sub>2<\/jats:sub>\n                      \/TP receptors in insulin resistance and lipid metabolism is largely unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      TP receptor knockout (TP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice were generated and fed a high\u2010fat diet for 16\u2009weeks. Insulin sensitivity, ER stress responses and hepatic lipid accumulation were assessed. Furthermore, we used primary hepatocytes to dissect the mechanisms by which the TXA\n                      <jats:sub>2<\/jats:sub>\n                      \/TP receptor axis regulates insulin signalling and hepatocyte lipogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      TXA\n                      <jats:sub>2<\/jats:sub>\n                      was increased in diet\u2010induced obese mice, and depletion of TP receptors in adult mice improved systemic insulin resistance and hepatic steatosis. Mechanistically, we found that the TXA\n                      <jats:sub>2<\/jats:sub>\n                      \/TP receptor axis disrupts insulin signalling by activating the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/calcium calmodulin\u2010dependent kinase II \u03b3 (CaMKII\u03b3)\u2013protein kinase RNA\u2010like endoplasmic reticulum kinase (PERK)\u2013C\/EBP homologous protein (Chop)\u2013tribbles\u2010like protein 3 (TRB3) axis in hepatocytes. In addition, our results revealed that the TXA\n                      <jats:sub>2<\/jats:sub>\n                      \/TP receptor axis directly promoted lipogenesis in primary hepatocytes and contributed to Kupffer cell inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      The TXA\n                      <jats:sub>2<\/jats:sub>\n                      \/TP receptor axis facilitates insulin resistance through Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CaMKII\u03b3 to activate PERK\u2013Chop\u2013TRB3 signalling. Inhibition of hepatocyte TP receptors improved hepatic steatosis and inflammation. The TP receptor is a new therapeutic target for NAFLD and metabolic syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16238","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T09:39:47Z","timestamp":1694597987000},"page":"967-986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Thromboxane A2\/thromboxane A2 receptor axis facilitates hepatic insulin resistance and steatosis through endoplasmic reticulum stress in non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"181","author":[{"given":"Yufeng","family":"Dai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijie","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"},{"name":"National Engineering Research Center for Functional Food Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-8679","authenticated-orcid":false,"given":"Haitao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Jiangnan University  Wuxi Jiangsu China"},{"name":"School of Food Science and Technology Jiangnan University  Wuxi Jiangsu China"},{"name":"National Engineering Research Center for Functional Food Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.011"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15541"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15542"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15539"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db20-1730-P"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db21-1213-P"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.06.010"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00675-6"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI153724"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20190083"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100086"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0659"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101300"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqac217"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079817"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115069"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09968"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106585"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2819-3"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2021.03.003"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2018.03.003"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.06.005"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108265"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2860-6"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32381"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11559"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(97)00322-0"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.06.008"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32708"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.015"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0379-5"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39112-6"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.01.001"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600596"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135846"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.10.011"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111015"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.03.002"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155516"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5053.1071"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.027538"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021110439"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.11.001"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1521"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.2100.760"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115465"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1893"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061620"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T01:06:00Z","timestamp":1710119160000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":54,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/bph.16238"],"URL":"https:\/\/doi.org\/10.1111\/bph.16238","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"assertion":[{"value":"2023-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}