{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:30:56Z","timestamp":1787027456266,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013279","name":"National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["2018ZX09711002\u2010002\u2010007"],"award-info":[{"award-number":["2018ZX09711002\u2010002\u2010007"]}],"id":[{"id":"10.13039\/501100013279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1302902"],"award-info":[{"award-number":["2022YFA1302902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22425703"],"award-info":[{"award-number":["22425703"]}],"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":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Obesity\u2010induced lipotoxicity is a key driver of pancreatic \u03b2\u2010cell dysfunction in Type 2 diabetes. Although Diacylglycerol O\u2010acyltransferase 1 (DGAT1) inhibition has been reported to ameliorate lipotoxic injury, the underlying mechanisms remain incompletely understood. This study leverages integrated proteomic and phosphoproteomic analyses to systematically explore the novel protective mechanisms of DGAT1 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed Min6 \u03b2\u2010cells subjected to palmitic acid (PA)\u2010induced lipotoxicity, comparing control, PA\u2010treated, and PA co\u2010treated with two distinct DGAT1 inhibitor groups. We assessed lipid accumulation, ER stress, and inflammation. Integrated proteomic and phosphoproteomic analyses, combined with bioinformatic interrogation and experimental validation, were employed to delineate novel molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DGAT1 inhibition effectively alleviated PA\u2010induced lipid deposition, ER stress, and inflammatory responses. Our multi\u2010omics data revealed that PA triggered ferroptosis, which was suppressed by DGAT1 inhibitors. Mechanistically, DGAT1 inhibition attenuated global O\u2010GlcNAcylation, leading to the destabilization of the pro\u2010ferroptotic protein ACSL4. This cascade resulted in reduced lipid peroxidation and restored glutathione levels, ultimately enhancing \u03b2\u2010cell survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study delineates the dynamic proteomic and phosphoproteomic landscape in Min6 cells under PA\u2010induced lipotoxicity and its remediation by a DGAT1 inhibitor. We delineate the remodelling of key signalling pathways, changes in critical gene expression, and dysregulation of transcription factor activity that collectively contribute to PA\u2010induced \u03b2\u2010cell injury. Furthermore, we reveal that DGAT1 inhibition attenuates ferroptosis through a novel mechanism involving DGAT1\u2010driven regulation of O\u2010GlcNAcylation. This study provides new insights into DGAT1 inhibition\u2010mediated protection against lipotoxicity and offers valuable multi\u2010omics data resources for the research community.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70554","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:36:16Z","timestamp":1771392976000},"page":"3716-3731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated proteomic and phosphoproteomic profiling unravels an O\u2010\n                    <scp>GlcNAc<\/scp>\n                    \u2010dependent mechanism in\n                    <scp>DGAT1<\/scp>\n                    inhibition\u2010mediated protection of \u03b2\u2010cells from lipotoxicity"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6725-9591","authenticated-orcid":false,"given":"Jia\u2010Ming","family":"Guo","sequence":"first","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research Shanghai Institute of Materia Media, Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences, Beijing  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang\u2010Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research Shanghai Institute of Materia Media, Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences, Beijing  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Shang","family":"Huang","sequence":"additional","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research Shanghai Institute of Materia Media, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Yun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research Shanghai Institute of Materia Media, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Yue","family":"Dong","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Fan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You\u2010Hong","family":"Hu","sequence":"additional","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research Shanghai Institute of Materia Media, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of 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