| First Author | Runtsch MC | Year | 2019 |
| Journal | PLoS Genet | Volume | 15 |
| Issue | 2 | Pages | e1007970 |
| PubMed ID | 30768595 | Mgi Jnum | J:273666 |
| Mgi Id | MGI:6282772 | Doi | 10.1371/journal.pgen.1007970 |
| Citation | Runtsch MC, et al. (2019) Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease. PLoS Genet 15(2):e1007970 |
| abstractText | Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-kappaB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes. |
