Scholarlink

<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 (m<sup>6</sup>A)-mediated RNA regulation in regulating hepatic mitochondrial function and fatty acid β-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 β-oxidation. Mechanistically, MCM3 increased NRF2 in hepatocytes by competitive combination with KEAP1. In addition, RBM15 overexpression accelerated m<sup>6</sup>A-YTHDF2-mediated <i>MCM3</i> mRNA decay. As expected, MCM3 knockdown negated the metabolic benefits of RBM15 knockdown. In conclusion, m<sup>6</sup>A-dependent MCM3 downregulation by RBM15/YTHDF2 impaired hepatic mitochondrial function and fatty acid β-oxidation in diabesity by reducing NRF2.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

RBM15 impairs Hepatic Mitochondria and β-Oxidation through m6A-dependent degradation of MCM3 mRNA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月18日

查看全文
  • Kai Chen,
  • Yi Xiang,
  • Daqing Deng,
  • Yingjie Zhang,
  • Xin Su,
  • Fang Hu

摘要

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 β-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 β-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 β-oxidation in diabesity by reducing NRF2.