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Published on: May 4, 2021
Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD-induced obesity by inhibiting PTEN
Juan Ji1,2, Yufeng Qin1,2, Jing Ren1,2
1State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Abstract:
Mitochondria-related microRNAs (miRNAs) have recently emerged as key regulators of cell metabolism and can modulate mitochondrial fusion and division. In order to investigate the roles of mitochondria-related miRNAs played in obesity, we conducted comprehensive molecular analysis in vitro and in vivo. Based on high-fat-diet (HFD) induced obese mice, we found that hepatic mitochondrial function was markedly altered. Subsequently, we evaluated the expression levels of selected mitochondria-related miRNAs and found that miR-141-3p was up-regulated strikingly in HFD mice. To further verify the role of miR-141-3p in obesity, we carried out gain-and-loss-of-function study in human HepG2 cells. We found that miR-141-3p could modulate ATP production and induce oxidative stress. Through luciferase report gene assay, we identified that phosphatase and tensin homolog (PTEN) was a target of miR-141-3p. Inhibiting PTEN could alter the mitochondrial function, too. Our study suggested that mitochondria-related miR-141-3p induced mitochondrial dysfunction by inhibiting PTEN.
Insights
Mitochondria-related microRNAs (miRNAs) like miR-141-3p are implicated in obesity. This study shows miR-141-3p impairs mitochondrial function by inhibiting PTEN, contributing to obesity-related metabolic dysfunction.
Area of Science:
- Cell Biology
- Metabolic Diseases
- Molecular Genetics
Background:
- Mitochondria-related microRNAs (miRNAs) regulate cell metabolism and mitochondrial dynamics.
- Obesity is associated with altered cellular metabolism and mitochondrial function.
Purpose of the Study:
- To investigate the role of mitochondria-related miRNAs in obesity.
- To elucidate the specific function of miR-141-3p in high-fat-diet induced obesity.
Main Methods:
- In vivo studies using high-fat-diet (HFD) induced obese mice.
- In vitro gain-and-loss-of-function studies in human HepG2 cells.
- Molecular analyses including miRNA expression profiling, ATP production assays, oxidative stress measurements, and luciferase reporter gene assays.
Main Results:
- Hepatic mitochondrial function was significantly altered in HFD mice.
- miR-141-3p was markedly up-regulated in HFD mice.
- miR-141-3p modulated ATP production, induced oxidative stress, and targeted phosphatase and tensin homolog (PTEN).
- Inhibition of PTEN also affected mitochondrial function.
Conclusions:
- Mitochondria-related miR-141-3p plays a significant role in obesity.
- miR-141-3p induces mitochondrial dysfunction by inhibiting PTEN.
- This miRNA-target interaction contributes to obesity-related metabolic alterations.
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