{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:18:21Z","timestamp":1792588701008,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202211010"],"award-info":[{"award-number":["SZSM202211010"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M761354"],"award-info":[{"award-number":["2024M761354"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471629"],"award-info":[{"award-number":["82471629"]}],"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":["82171583"],"award-info":[{"award-number":["82171583"]}],"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":["82301748"],"award-info":[{"award-number":["82301748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The rising global prevalence of obesity has accelerated the incidence of metabolic dysfunction\u2010associated steatotic liver disease (MASLD), with nonalcoholic steatohepatitis (NASH) representing its progressive and life\u2010threatening phenotype. Despite its clinical urgency, no pharmacotherapy is currently approved for NASH. AdipoRon, an orally active adiponectin receptor agonist, exhibits dual regulatory effects on glucose\/lipid homeostasis alongside anti\u2010inflammatory and antioxidant properties. However, its therapeutic potential in metabolic stress\u2010driven NASH remains underexplored. This study elucidates the efficacy and molecular mechanisms of AdipoRon in mitigating metabolic stress\u2010induced NASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We employed a multi\u2010modal approach combining in vitro and in vivo models: palmitic acid (PA)\u2010challenged alpha mouse liver 12 (AML12) hepatocytes and mice fed a Western diet (WD) or a methionine\u2010choline\u2010deficient (MCD) diet. Proteomic profiling integrated with bioinformatics analysis was utilized to dissect AdipoRon's mechanism. Pharmacological validation via endoplasmic reticulum (ER) stress modulation (e.g., cinchonine) further clarified pathway specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, AdipoRon attenuated PA\u2010induced lipid accumulation and inflammatory cytokine release in hepatocytes. In vivo, AdipoRon administration markedly reduced hepatic injury, steatosis, lobular inflammation and collagen deposition in diet\u2010induced NASH mice. Mechanistically, proteomic analysis identified ER stress suppression as a central pathway, with rescue experiments confirming that cinchonine (an ER stress activator) abrogated AdipoRon's hepatoprotection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings establish AdipoRon as a potent inhibitor of ER stress, effectively counteracting metabolic stress\u2010induced NASH pathogenesis. These results highlight its translational promise as a targeted therapy for NASH, addressing critical unmet clinical needs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16542","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:56:59Z","timestamp":1751194619000},"page":"4950-4967","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>AdipoRon<\/scp>\n                    attenuates steatosis, inflammation and fibrosis in murine diet\u2010induced\n                    <scp>NASH<\/scp>\n                    via inhibiting\n                    <scp>ER<\/scp>\n                    stress"],"prefix":"10.1111","volume":"27","author":[{"given":"Lulin","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital)  Dongguan China"},{"name":"Shenzhen Key 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