| First Author | Jia Y | Year | 2023 |
| Journal | Obesity (Silver Spring) | Volume | 31 |
| Issue | 12 | Pages | 2972-2985 |
| PubMed ID | 37752619 | Mgi Jnum | J:344869 |
| Mgi Id | MGI:7579436 | Doi | 10.1002/oby.23884 |
| Citation | Jia Y, et al. (2023) MiR-484 promotes nonalcoholic fatty liver disease progression in mice via downregulation of Sorbs2. Obesity (Silver Spring) 31(12):2972-2985 |
| abstractText | OBJECTIVE: MicroRNA 484 (miR-484) plays a pivotal role in the development and progression of different diseases and is typically described as a mitochondrial regulator. Whether miR-484 is involved in lipid metabolism or exerts a role in nonalcoholic fatty liver disease remains unclear. METHODS: miR-484 levels were examined in the livers of male mice fed a high-fat diet and in hepatocytes treated with free fatty acids. Sorbin and SH3 structural domain-containing protein 2 (Sorbs2) were identified as a novel target of miR-484 by sequencing mRNA in the livers of miR-484 knockout mice. Sorbs2 liver-specific knockdown mice were constructed by tail vein injection of adeno-associated virus vector to miR-484 knockout mice. In addition, genetic manipulation of SORBS2 was performed in human hepatocyte lines, mouse primary hepatocytes, and the liver. RESULTS: Serum and hepatic miR-484 levels are upregulated in nonalcoholic fatty liver disease mice. miR-484 knockdown ameliorated hepatocyte steatosis, whereas miR-484 overexpression increased hepatocyte lipid load. miR-484 knockdown-mediated alleviation of hepatic steatosis, liver injury, inflammation, and apoptosis was compromised after high-fat diet-induced knockdown of Sorbs2 in mouse liver and free fatty acid-induced primary mouse hepatocytes. CONCLUSIONS: These results identify Sorbs2-mediated mitochondrial beta-oxidation and apoptosis that promote miR-484 knockdown-mediated remission of hepatic steatosis. |
