| First Author | Kineman RD | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 5 | Pages | 1728-35 |
| PubMed ID | 26950202 | Mgi Jnum | J:234559 |
| Mgi Id | MGI:5790267 | Doi | 10.1210/en.2015-2077 |
| Citation | Kineman RD, et al. (2016) Hepatic PPARgamma Is Not Essential for the Rapid Development of Steatosis After Loss of Hepatic GH Signaling, in Adult Male Mice. Endocrinology 157(5):1728-35 |
| abstractText | Our group has previously reported de novo lipogenesis (DNL) and hepatic triglyceride content increases in chow-fed male mice within 7 days of hepatocyte-specific GH receptor knockdown (aLivGHRkd). Here, we report that these changes are associated with an increase in hepatic expression of peroxisome proliferator-activated receptor gamma (PPARgamma), consistent with previous reports showing steatosis is associated with an increase in PPARgamma expression in mice with congenital loss of hepatic GH signaling. PPARgamma is thought to be an important driver of steatosis by enhancing DNL, as well as increasing the uptake and esterification of extrahepatic fatty acids (FAs). In order to determine whether hepatic PPARgamma is critical for the rapid development of steatosis in the aLivGHRkd mouse model, we have generated aLivGHRkd mice, with or without PPARgamma (ie, adult-onset, hepatocyte-specific double knockout of GHR and PPARgamma). Hepatic PPARgamma was not required for the rapid increase in liver triglyceride content or FA indexes of DNL (16:0/18:2 and 16:1/16:0). However, loss of hepatic PPARgamma blunted the rise in fatty acid translocase/CD36 and monoacylglycerol acyltransferase 1 expression induced by aLivGHRkd, and this was associated with a reduction in the hepatic content of 18:2. These results suggest that the major role of PPARgamma is to enhance pathways critical in uptake and reesterification of extrahepatic FA. Because FAs have been reported to directly increase PPARgamma expression, we speculate that in the aLivGHRkd mouse, the FA produced by DNL enhances the expression of PPARgamma, which in turn increases extrahepatic FA uptake, thereby further enhancing PPARgamma activity and exacerbating steatosis overtime. |
