| First Author | Qu X | Year | 2022 |
| Journal | Clin Transl Med | Volume | 12 |
| Issue | 9 | Pages | e1061 |
| PubMed ID | 36149763 | Mgi Jnum | J:330146 |
| Mgi Id | MGI:7365320 | Doi | 10.1002/ctm2.1061 |
| Citation | Qu X, et al. (2022) PARK7 deficiency inhibits fatty acid beta-oxidation via PTEN to delay liver regeneration after hepatectomy. Clin Transl Med 12(9):e1061 |
| abstractText | BACKGROUND & AIMS: Transient regeneration-associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid beta-oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism-associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high-fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknown METHODS: Park7 knockout (Park7(-/-) ), hepatocyte-specific Park7 knockout (Park7( big up tri, openhep) ) and hepatocyte-specific Park7-Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx) RESULTS: Increased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx. Park7(-/-) and Park7( big up tri, openhep) mice showed delayed liver regeneration and enhanced TRAS after PHx. PPARa, a key regulator of beta-oxidation, and carnitine palmitoyltransferase 1a (CPT1a), a rate-limiting enzyme of beta-oxidation, had substantially decreased expression in the regenerating liver of Park7( big up tri, openhep) mice. Increased phosphatase and tensin homolog (PTEN) expression was observed in the liver of Park7( big up tri, openhep) mice, which might contribute to delayed liver regeneration in these mice because genomic depletion or pharmacological inhibition of PTEN restored the delayed liver regeneration by reversing the downregulation of PPARa and CPT1a and in turn accelerating the utilization of TRAS in the regenerating liver of Park7( big up tri, openhep) mice CONCLUSION: Park7/Dj1 is a novel regulator of PTEN-dependent fatty acid beta-oxidation, and increasing Park7 expression might be a promising strategy to promote liver regeneration. |
