| First Author | Flach RJ | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 25 | Pages | 22195-202 |
| PubMed ID | 21521693 | Mgi Jnum | J:174820 |
| Mgi Id | MGI:5141205 | Doi | 10.1074/jbc.M110.210237 |
| Citation | Flach RJ, et al. (2011) Loss of mitogen-activated protein kinase phosphatase-1 protects from hepatic steatosis by repression of cell death-inducing DNA fragmentation factor A (DFFA)-like effector C (CIDEC)/fat-specific protein 27. J Biol Chem 286(25):22195-202 |
| abstractText | The integration of metabolic signals required for the regulation of hepatic lipid homeostasis is complex. Previously, we showed that mice lacking expression of the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) have increased fatty acid oxidation and are protected from the development of hepatic steatosis. Here, we show that leptin receptor-deficient (db/db) mice lacking MKP-1 are also resistant to the development of hepatic steatosis. Microarray analyses of livers from db/db mice lacking MKP-1 showed suppression of peroxisome proliferator-activated receptor gamma (PPARgamma) target genes. We identified the fat-specific protein 27 (Fsp27), which promotes PPARgamma-mediated hepatic steatosis, as repressed in livers of both db/db and high fat diet-fed mice lacking MKP-1. Hepatocytes from MKP-1-deficient mice exhibited reduced PPARgamma-induced lipid droplet formation. Mechanistically, loss of MKP-1 inhibited PPARgamma function by increasing MAPK-dependent phosphorylation on PPARgamma at its inhibitory residue of serine 112. These results demonstrate that in addition to inhibiting hepatic fatty acid oxidation, MKP-1 promotes hepatic lipogenic gene expression through PPARgamma. Hence, MKP-1 plays an important role in MAPK-mediated control of hepatic lipid homeostasis. |
