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An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Published on: April 26, 2019
Changes of m6A Regulatory Proteins and Nrf2 Signaling Molecules in Liver Tissue of Type 2 Diabetes Mellitus Rats
Nan Wang1, Jie Yang2, Xiaoyu Liu1
1Institute of Preventive Medicine, School of Public Health, Dali University, No. 22, Wanhua Road, Dali, Yunnan, 671000, China.
Abstract:
Both dysregulation of N6-methyladenosine (m6A) regulatory proteins and Nrf2 signaling molecules are involved in the process of injury to multiple tissues. However, changes of m6A regulatory proteins and Nrf2 signaling molecules in liver tissue of T2DM remain unclear. In present study, changes of m6A regulatory proteins (Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2) and Nrf2 signaling molecules (Nrf2, Sod1, Ho-1, Gclc) were detected in the liver tissues of T2DM rats, which constructed by high fat-diet feeding and intraperitoneal injection of streptozotocin. Our results indicated that the morphology of liver tissues from T2DM rats showed obvious abnormalities, as well as levels of liver function indicators and expressions of Nrf2 signaling molecules Nrf2, Sod1, Ho-1 were significantly increased in T2DM rats when compared with those in corresponding control rats. More importantly, m6A regulatory proteins such as Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2 were dramatically higher than those in control rat. In a word, m6A regulatory proteins and Nrf2 signaling molecules may significantly change in liver tissue of T2DM rats. And This provides clues and ideas for the study of liver injury in T2DM from the perspective of RNA epigenetics in the future.
Insights
Changes in RNA epigenetic regulators and Nrf2 signaling molecules were observed in the liver tissue of type 2 diabetes mellitus (T2DM) rats. These findings offer new insights into liver injury mechanisms in T2DM.
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- Dysregulation of N6-methyladenosine (m6A) regulatory proteins and Nrf2 signaling molecules are implicated in tissue injury.
- The specific alterations in these pathways within the liver of type 2 diabetes mellitus (T2DM) remain largely uncharacterized.
Purpose of the Study:
- To investigate the changes in m6A regulatory proteins and Nrf2 signaling molecules in the liver tissue of T2DM rats.
- To explore the potential role of RNA epigenetics in T2DM-related liver injury.
Main Methods:
- A T2DM rat model was established using a high-fat diet and streptozotocin injection.
- Levels of m6A regulatory proteins (Mettl3, Mettl16, Fto, Alkbh5, Ythdc2) and Nrf2 signaling molecules (Nrf2, Sod1, Ho-1, Gclc) were assessed in liver tissues.
Main Results:
- T2DM rat livers exhibited morphological abnormalities and altered liver function indicators.
- Expressions of Nrf2 signaling molecules (Nrf2, Sod1, Ho-1) were significantly increased in T2DM rats.
- Levels of m6A regulatory proteins (Mettl3, Mettl16, Fto, Alkbh5, Ythdc2) were dramatically elevated in T2DM rat livers compared to controls.
Conclusions:
- Significant alterations in m6A regulatory proteins and Nrf2 signaling molecules occur in the liver of T2DM rats.
- These findings suggest a potential link between RNA epigenetics and liver injury in T2DM.
- This study provides a foundation for future research into T2DM liver injury from an RNA epigenetic perspective.

