Downregulation of the DNA 5-hydroxymethylcytosine is involved in mitochondrial dysfunction and neuronal impairment in high fat diet-induced diabetic mice

Run Liu, Lei Chen, Zhen Wang, Xuewei Zheng, Yan Wang, Hua Li, Mami Noda, Jiankang Liu, Jiangang Long

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

DNA 5-hydroxymethylcytosine (5hmC), converted from 5-methylcytosine (5mC), is highly enriched in the central nervous system and is dynamically regulated during neural development and metabolic disorders. However, whether and how neural 5hmC is involved in metabolic disorders shows little evidence. In this study, significant downregulation of the DNA 5hmC were observed in the cerebral cortex of HFD-induced diabetic mice, while phosphated AMP-activated protein kinase (p-AMPK) and ten-eleven translocation 2 (TET2) reduced, and mitochondrial dysfunction. We futher demonstrated that dysregulation of 5hmC preceded mitochondrial dysfunction in palmitic acid-treated HT22 cells and decreased level of 5hmC led to mitochondrial respiratory activity and apoptosis in HT22 cells. Taken together, our results reveal that neural 5hmC undergoes remodeling during HFD-induced metabolic disorder, and 5hmC downregulation significantly impacts on mitochondrial respiration and cell apoptosis. This study suggests a novel link between metabolic disorder and neural impairment through neural DNA 5hmC remodeling and resultant mitochondrial dysfunction.

本文言語英語
ページ(範囲)42-51
ページ数10
ジャーナルFree Radical Biology and Medicine
148
DOI
出版ステータス出版済み - 2 20 2020

All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学(医学)

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