Fenofibrate-promoted hepatomegaly and liver regeneration are PPAR<i>α</i>-dependent and partially related to the YAP pathway.

ABSTRACT: Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and tran

SUBMITTER: Fan S 

PROVIDER: S-EPMC11252459 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature