{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:10:12Z","timestamp":1780384212704,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity\u2010related insulin resistance (IR) involves mitochondrial dysfunction and ferroptosis dysregulation. Ubiquitin\u2010like with PHD and RING finger domains 1 (UHRF1), an epigenetic regulator of DNA methylation, mediates crucial functions in disease progression, though its mechanisms in IR remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using murine IR models and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1)\u2010induced adipocyte systems, UHRF1's regulation of mitophagy and ferroptosis was assessed. Bioinformatics identified downstream targets Kelch\u2010like protein 6 (KLHL6) and coronin 2B (CORO2B), prompting examination of the UHRF1\u2010KLHL6\u2010CORO2B axis in obesity\u2010related IR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Obesity\u2010related IR mice exhibited increased body weight, impaired glucose and insulin tolerance, adipose tissue inflammation, impaired mitophagy, and alterations in ferroptosis\u2010related parameters, accompanied by reduced UHRF1 expression.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , TNF\u2010\u03b1\u2010treated adipocytes showed decreased mitophagy, elevated oxidative stress, and changes consistent with ferroptosis, along with lower UHRF1 levels. UHRF1 overexpression was associated with changes in PINK1\/Parkin\u2010related markers, cell viability, oxidative stress indicators, ferroptosis\u2010related parameters, and inflammatory responses. UHRF1 overexpression was associated with increased KLHL6 DNA methylation, decreased KLHL6 expression, and alterations in CORO2B ubiquitination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>UHRF1 overexpression was associated with decreased KLHL6 expression, altered CORO2B ubiquitination, and changes in autophagy\u2010, ferroptosis\u2010, and inflammation\u2010related markers. These results provide insights into potential pathogenic mechanisms and suggest that UHRF1, KLHL6, and CORO2B may serve as candidate targets for further investigation in obesity\u2010related IR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70291","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:51:32Z","timestamp":1774957892000},"page":"920-937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of the\n                    <scp>UHRF1<\/scp>\n                    \u2013\n                    <scp>KLHL6<\/scp>\n                    \u2013\n                    <scp>CORO2B<\/scp>\n                    axis in obesity\u2010related insulin resistance"],"prefix":"10.1111","volume":"17","author":[{"given":"Xu","family":"Deng","sequence":"first","affiliation":[{"name":"Center of Preventive Treatment of Disease The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Preventive Treatment of Disease The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialuo","family":"Cai","sequence":"additional","affiliation":[{"name":"Center of Preventive Treatment of Disease The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Preventive Treatment of Disease The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Preventive Treatment of Disease The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8640-1137","authenticated-orcid":false,"given":"Yuntao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Health Management The First Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-022-01729-9"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051305"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-018-0481-6"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1019"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.153048"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10010065"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10142-022-00918-9"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2023.14129"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-62508-y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018752"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1568765"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13099-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45303-y"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-05076-0"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-019-0914-1"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/21623945.2020.1778826"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12747"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13041302"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.11.012"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.03.003"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317692205"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0810-7"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00565-y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.14712\/fb2022068050189"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.15026"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1522912"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-813139"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2017.11.001"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15844-1"}],"container-title":["Journal 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