{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:21Z","timestamp":1792384881102,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070842"],"award-info":[{"award-number":["82070842"]}],"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":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endothelial dysfunction induced by elevated free fatty acids is a critical initiating event in diabetic macrovascular complications. While mitochondrial reactive oxygen species (mtROS) are key mediators of this lipotoxic injury, the\u00a0specific contribution of mitochondrial Complex I dynamics and its associated redox regulation remains to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the therapeutic potential of targeting mitochondrial Complex I in lipotoxicity\u2010induced endothelial injury. Using rotenone (a Complex I inhibitor) and\n                      <jats:italic>NDUFS4<\/jats:italic>\n                      [NADH Dehydrogenase (Ubiquinone) Fe\u2010S Protein 4]\u2010targeting siRNA, we performed in\u00a0vitro interventions in palmitic acid\u2010treated human aortic endothelial cells and in\u00a0vivo studies in high\u2010fat diet (HFD)\u2010fed mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Palmitic acid triggered endothelial dysfunction accompanied by pronounced mitochondrial oxidative stress. Mechanistically, palmitic acid lowered the oxidised\/reduced nicotinamide adenine dinucleotide (NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH) ratio and increased NADH\u2010linked Complex I activity, a redox state consistent with enhanced Complex I\u2010linked ROS generation. Pharmacological (rotenone) or genetic (\n                      <jats:italic>NDUFS4<\/jats:italic>\n                      knockdown) modulation of Complex I activity suppressed mtROS overproduction, improved NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH balance, alleviated oxidative stress and improved endothelial function. In\u00a0vivo, rotenone attenuated HFD\u2010induced systemic metabolic disturbances and vascular oxidative stress while improving endothelial barrier integrity and angiogenic responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study suggests that dysregulated mitochondrial Complex I activity may serve as an important contributor to lipotoxic endothelial injury. These findings support Complex I modulation as a potential strategy to mitigate free fatty acid\u2010induced endothelial dysfunction in obesity\u2010 and diabetes\u2010related vascular complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71164","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:07:33Z","timestamp":1786327653000},"page":"9880-9896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Mitochondrial Complex I Protects Against Palmitic Acid\u2013Induced Endothelial Dysfunction"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5439-2515","authenticated-orcid":false,"given":"Chenxia","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology Shanghai East Hospital, Tongji University School of Medicine  Shanghai 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