Hepatocyte Peroxisome Proliferator-Activated Receptor ? Enhances Liver Regeneration after Partial Hepatectomy in Mice.

ABSTRACT: Peroxisome proliferator-activated receptor ? (PPAR?) is a key nuclear receptor involved in the control of lipid homeostasis. In rodents, PPAR? is also a potent hepatic mitogen. Hepatocyte-specific disruption of PPAR? inhibits agonist-induced hepatocyte proliferation; however, little is known about the exact role of PPAR? in partial hepatectomy (PHx)-induced liver regeneration. Herein, using hepatocyte-specific PPAR?-deficient (Ppara?Hep) mice, the function of hepatocyte PPAR? in PHx-induced liver regeneration was investigated. PPAR? protein level and transcriptional activity were increased in the liver after PHx. Compared with the Pparafl/fl mice, Ppara?Hep mice exhibited significantly reduced hepatocyte proliferation at 32 hours after PHx. Consistently, reduced Ccnd1 and Pcna mRNA and CYCD1 and proliferating cell nuclear antigen protein were observed at 32 hours after PHx in Ppara?Hep mice. Furthermore, Ppara?Hep mice showed increased hepatic lipid accumulation and enhanced hepatic triglyceride contents because of impaired hepatic fatty acid ?-oxidation when compared with that observed in Pparafl/fl mice. These results indicate that PPAR? promotes liver regeneration after PHx, at least partially via regulating the cell cycle and lipid metabolism.

SUBMITTER: Xie G 

PROVIDER: S-EPMC6593252 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature