Hepatocyte Peroxisome Proliferator–Activated Receptor α Enhances Liver Regeneration after Partial Hepatectomy in Mice

Guomin Xie, Shi Yin, Zhenzhen Zhang, Dan Qi, Xia Wang, Donghwan Kim, Tomoki Yagai, Chad N. Brocker, Yan Wang, Frank J. Gonzalez, Hua Wang, Aijuan Qu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)272-282
Number of pages11
JournalAmerican Journal of Pathology
Volume189
Issue number2
DOIs
Publication statusPublished - 2019 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Hepatocyte Peroxisome Proliferator–Activated Receptor α Enhances Liver Regeneration after Partial Hepatectomy in Mice'. Together they form a unique fingerprint.

Cite this