{"id":533157,"date":"2026-07-19T04:30:28","date_gmt":"2026-07-19T04:30:28","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/533157\/"},"modified":"2026-07-19T04:30:28","modified_gmt":"2026-07-19T04:30:28","slug":"rbm15-impairs-hepatic-mitochondria-and-%ce%b2-oxidation-through-m6a-dependent-degradation-of-mcm3-mrna","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/533157\/","title":{"rendered":"RBM15 impairs Hepatic Mitochondria and \u03b2-Oxidation through m6A-dependent degradation of MCM3 mRNA"},"content":{"rendered":"<p>Diabesity, defined as obesity accompanied by Type 2 diabetes mellitus, is characterized by metabolic dysfunction and mitochondrial impairment. Here, we investigate the role of N6-methyladenosine (m6A)-mediated RNA regulation in regulating hepatic mitochondrial function and fatty acid \u03b2-oxidation during diabesity progression. Diabesity was modeled in male C57BLKS\/J db\/db mice, with db\/m lean mice as controls; in vitro models were established using primary hepatocytes isolated from male C57BL\/6J mice exposed to high glucose and palmitate. Our results showed that MCM3 was significantly downregulated in diabesity models. MCM3 overexpression improved hepatic mitochondrial function and fatty acid \u03b2-oxidation. Mechanistically, MCM3 increased NRF2 in hepatocytes by competitive combination with KEAP1. In addition, RBM15 overexpression accelerated m6A-YTHDF2-mediated MCM3 mRNA decay. As expected, MCM3 knockdown negated the metabolic benefits of RBM15 knockdown. In conclusion, m6A-dependent MCM3 downregulation by RBM15\/YTHDF2 impaired hepatic mitochondrial function and fatty acid \u03b2-oxidation in diabesity by reducing NRF2.<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/www.newsbeep.com\/nz\/wp-content\/uploads\/2026\/07\/42003_2026_10673_Figa_HTML.png\" alt=\"\" loading=\"lazy\" width=\"685\" height=\"461\"\/><\/p>\n","protected":false},"excerpt":{"rendered":"Diabesity, defined as obesity accompanied by Type 2 diabetes mellitus, is characterized by metabolic dysfunction and mitochondrial impairment.&hellip;\n","protected":false},"author":2,"featured_media":533158,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[2480,5300,2294,6422,111,139,69,147],"class_list":["post-533157","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-cardiovascular-diseases","tag-cell-biology","tag-general","tag-life-sciences","tag-new-zealand","tag-newzealand","tag-nz","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/533157","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=533157"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/533157\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/533158"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=533157"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=533157"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=533157"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}