| First Author | Konstandi M | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e70675 |
| PubMed ID | 23967086 | Mgi Jnum | J:206357 |
| Mgi Id | MGI:5550059 | Doi | 10.1371/journal.pone.0070675 |
| Citation | Konstandi M, et al. (2013) Role of PPARalpha and HNF4alpha in stress-mediated alterations in lipid homeostasis. PLoS One 8(8):e70675 |
| abstractText | Stress is a risk factor for several cardiovascular pathologies. PPARalpha holds a fundamental role in control of lipid homeostasis by directly regulating genes involved in fatty acid transport and oxidation. Importantly, PPARalpha agonists are effective in raising HDL-cholesterol and lowering triglycerides, properties that reduce the risk for cardiovascular diseases. This study investigated the role of stress and adrenergic receptor (AR)-related pathways in PPARalpha and HNF4alpha regulation and signaling in mice following repeated restraint stress or treatment with AR-antagonists administered prior to stress to block AR-linked pathways. Repeated restraint stress up-regulated Pparalpha and its target genes in the liver, including Acox, Acot1, Acot4, Cyp4a10, Cyp4a14 and Lipin2, an effect that was highly correlated with Hnf4alpha. In vitro studies using primary hepatocyte cultures treated with epinephrine or AR-agonists confirmed that hepatic AR/cAMP/PKA/CREB- and JNK-linked pathways are involved in PPARalpha and HNF4alpha regulation. Notably, restraint stress, independent of PPARalpha, suppressed plasma triglyceride levels. This stress-induced effect could be attributed in part to hormone sensitive lipase activation in the white adipose tissue, which was not prevented by the increased levels of perilipin. Overall, this study identifies a mechanistic basis for the modification of lipid homeostasis following stress and potentially indicates novel roles for PPARalpha and HNF4alpha in stress-induced lipid metabolism. |
