| First Author | Roos J | Year | 2021 |
| Journal | Cell Mol Life Sci | Volume | 78 |
| Issue | 6 | Pages | 2987-3003 |
| PubMed ID | 33206203 | Mgi Jnum | J:307558 |
| Mgi Id | MGI:6705773 | Doi | 10.1007/s00018-020-03699-1 |
| Citation | Roos J, et al. (2021) miR-146a regulates insulin sensitivity via NPR3. Cell Mol Life Sci 78(6):2987-3003 |
| abstractText | The pathogenesis of obesity-related metabolic diseases has been linked to the inflammation of white adipose tissue (WAT), but the molecular interconnections are still not fully understood. MiR-146a controls inflammatory processes by suppressing pro-inflammatory signaling pathways. The aim of this study was to characterize the role of miR-146a in obesity and insulin resistance. MiR-146a(-/-) mice were subjected to a high-fat diet followed by metabolic tests and WAT transcriptomics. Gain- and loss-of-function studies were performed using human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Compared to controls, miR-146a(-/-) mice gained significantly more body weight on a high-fat diet with increased fat mass and adipocyte hypertrophy. This was accompanied by exacerbated liver steatosis, insulin resistance, and glucose intolerance. Likewise, adipocytes transfected with an inhibitor of miR-146a displayed a decrease in insulin-stimulated glucose uptake, while transfecting miR-146a mimics caused the opposite effect. Natriuretic peptide receptor 3 (NPR3) was identified as a direct target gene of miR-146a in adipocytes and CRISPR/Cas9-mediated knockout of NPR3 increased insulin-stimulated glucose uptake and enhanced de novo lipogenesis. In summary, miR-146a regulates systemic and adipocyte insulin sensitivity via downregulation of NPR3. |
