| First Author | Alé A | Year | 2017 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 312 |
| Issue | 3 | Pages | E161-E174 |
| PubMed ID | 27894066 | Mgi Jnum | J:244336 |
| Mgi Id | MGI:5913115 | Doi | 10.1152/ajpendo.00337.2016 |
| Citation | Ale A, et al. (2017) Obesity-associated extracellular mtDNA activates central TGFbeta pathway to cause blood pressure increase. Am J Physiol Endocrinol Metab 312(3):E161-E174 |
| abstractText | Hypothalamic inflammation was recently found to mediate obesity-related hypertension, but the responsible upstream mediators remain unexplored. In this study, we show that dietary obesity is associated with extracellular release of mitochondrial DNA (mtDNA) into the cerebrospinal fluid and that central delivery of mtDNA mimics transforming growth factor-beta (TGFbeta) excess to activate downstream signaling pathways. Physiological study reveals that central administration of mtDNA or TGFbeta is sufficient to cause hypertension in mice. Knockout of the TGFbeta receptor in proopiomelanocortin neurons counteracts the hypertensive effect of not only TGFbeta but also mtDNA excess, while the hypertensive action of central mtDNA can be blocked pharmacologically by a TGFbeta receptor antagonist or genetically by TGFbeta receptor knockout. Finally, we confirm that obesity-induced hypertension can be reversed through central treatment with TGFbeta receptor antagonist. In conclusion, circulating mtDNA in the brain employs neural TGFbeta pathway to mediate a central inflammatory mechanism of obesity-related hypertension. |
