{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T23:21:37Z","timestamp":1767136897567,"version":"build-2238731810"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T00:00:00Z","timestamp":1644710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M692125"],"award-info":[{"award-number":["2021M692125"]}],"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":["81770797"],"award-info":[{"award-number":["81770797"]}],"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":["82170863"],"award-info":[{"award-number":["82170863"]}],"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":["8210115383"],"award-info":[{"award-number":["8210115383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002857","name":"China Pharmaceutical University","doi-asserted-by":"publisher","award":["SKLNMKF201706"],"award-info":[{"award-number":["SKLNMKF201706"]}],"id":[{"id":"10.13039\/501100002857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002857","name":"China Pharmaceutical University","doi-asserted-by":"publisher","award":["SKLNMZZCX201820"],"award-info":[{"award-number":["SKLNMZZCX201820"]}],"id":[{"id":"10.13039\/501100002857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["21QA1407000"],"award-info":[{"award-number":["21QA1407000"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Receptor\u2010interacting serine\/threonine\u2010protein kinase 1 (RIP1) is a well\u2010documented key regulator of TNF\u03b1\u2010mediated inflammation, apoptosis, and necroptosis, which contribute to the development of obesity\u2010related metabolic diseases such as nonalcoholic steatohepatitis. However, the mechanism regarding how RIP1 influences obesity\u2010related insulin resistance remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary hepatocytes with necrostatin 1 treatment or RIP1 expression were exposed to palmitic acid (PA), prior to the examination of cellular insulin signaling. Phosphorylation sites of RIP1 were detected by liquid chromatography with tandem mass spectrometry, and RIP1 variants with mutated phosphorylation sites were overexpressed in hepatocytes to identify the specific residue that influenced the RIP1\u2010mediated insulin resistance. Adenovirus expressing RIP1 (S415A) mutant were administered into diet\u2010induced obese mice to assess the effects on insulin sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study uncovered an aberrant increase in RIP1 activity during the development of obesity\u2010induced insulin resistance. Inhibition of RIP1 activity with necrostatin 1 ameliorated PA\u2010 or high\u2010fat diet\u2010caused hepatic insulin resistance. With liquid chromatography with tandem mass spectrometry analysis and mutagenesis screening, S415, a novel phosphorylation site of RIP1, was identified to be responsible for RIP1\u2010mediated insulin resistance. Loss\u2010of\u2010function mutation of S415 efficiently blunted RIP1\u2010evoked insulin resistance in PA\u2010treated hepatocytes or diet\u2010induced obese mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight the diabetogenic role of RIP1 S415 and propose RIP1 as a promising therapeutic target for type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/oby.23361","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T23:19:05Z","timestamp":1644794345000},"page":"680-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Suppression of RIP1 activity via S415 dephosphorylation ameliorates obesity\u2010related hepatic insulin resistance"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-5961","authenticated-orcid":false,"given":"Yanping","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Diabetes Mellitus Shanghai Diabetes Institute Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Diabetes Mellitus Shanghai Diabetes Institute Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory 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