| First Author | Greene MW | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e85848 |
| PubMed ID | 24454937 | Mgi Jnum | J:212187 |
| Mgi Id | MGI:5578273 | Doi | 10.1371/journal.pone.0085848 |
| Citation | Greene MW, et al. (2014) Lipid metabolism, oxidative stress and cell death are regulated by PKC delta in a dietary model of nonalcoholic steatohepatitis. PLoS One 9(1):e85848 |
| abstractText | Steatosis, oxidative stress, and apoptosis underlie the development of nonalcoholic steatohepatitis (NASH). Protein kinase C delta (PKCdelta) has been implicated in fatty liver disease and is activated in the methionine and choline-deficient (MCD) diet model of NASH, yet its pathophysiological importance towards steatohepatitis progression is uncertain. We therefore addressed the role of PKCdelta in the development of steatosis, inflammation, oxidative stress, apoptosis, and fibrosis in an animal model of NASH. We fed PKCdelta(-/-) mice and wildtype littermates a control or MCD diet. PKCdelta(-/-) primary hepatocytes were used to evaluate the direct effects of fatty acids on hepatocyte lipid metabolism gene expression. A reduction in hepatic steatosis and triglyceride levels were observed between wildtype and PKCdelta(-/-) mice fed the MCD diet. The hepatic expression of key regulators of beta-oxidation and plasma triglyceride metabolism was significantly reduced in PKCdelta(-/-) mice and changes in serum triglyceride were blocked in PKCdelta(-/-) mice. MCD diet-induced hepatic oxidative stress and hepatocyte apoptosis were reduced in PKCdelta(-/-) mice. MCD diet-induced NADPH oxidase activity and p47(phox) membrane translocation were blunted and blocked, respectively, in PKCdelta(-/-) mice. Expression of pro-apoptotic genes and caspase 3 and 9 cleavage in the liver of MCD diet fed PKCdelta(-/-) mice were blunted and blocked, respectively. Surprisingly, no differences in MCD diet-induced fibrosis or pro-fibrotic gene expression were observed in 8 week MCD diet fed PKCdelta(-/-) mice. Our results suggest that PKCdelta plays a role in key pathological features of fatty liver disease but not ultimately in fibrosis in the MCD diet model of NASH. |
