{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:19:49Z","timestamp":1792653589157,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T00:00:00Z","timestamp":1500508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T00:00:00Z","timestamp":1500508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>In regenerating liver, hepatocytes accumulate lipids before the major wave of parenchymal growth. This transient, regeneration\u2010associated steatosis (TRAS) is required for liver recovery, but its purpose is unclear. The tumor suppressor phosphatase and tensin homolog (PTEN) is a key inhibitor of the protein kinase B\/mammalian target of rapamycin axis that regulates growth and metabolic adaptations after hepatectomy. In quiescent liver, PTEN causes pathological steatosis when lost, whereas its role in regenerating liver remains unknown. Here, we show that PTEN down\u2010regulation promotes liver growth in a TRAS\u2010dependent way. In wild\u2010type mice, PTEN reduction occurred after TRAS formation, persisted during its disappearance, and correlated with up\u2010regulated \u03b2\u2010oxidation at the expense of lipogenesis. Pharmacological modulation revealed an association of PTEN with TRAS turnover and hypertrophic liver growth. In liver\u2010specific<jats:italic toggle=\"yes\">Pten<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>mice shortly after induction of knockout, hypertrophic regeneration was accelerated and led to hepatomegaly. The resulting surplus liver mass was functional, as demonstrated by raised survival in a lethal model of resection\u2010induced liver failure. Indirect calorimetry revealed lipid oxidation as the primary energy source early after hepatectomy. The shift from glucose to lipid usage was pronounced in<jats:italic toggle=\"yes\">Pten\u2013\/\u2013<\/jats:italic>mice and correlated with the disappearance of TRAS. Partial inhibition of \u03b2\u2010oxidation led to persisting TRAS in<jats:italic toggle=\"yes\">Pten<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>mice and abrogated hypertrophic liver growth. PTEN down\u2010regulation may promote \u03b2\u2010oxidation through \u03b2\u2010catenin, whereas hypertrophy was dependent on mammalian target of rapamycin complex 1.<jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: PTEN down\u2010regulation after hepatectomy promotes the burning of TRAS\u2010derived lipids to fuel hypertrophic liver regeneration. Therefore, the anabolic function of PTEN deficiency in resting liver is transformed into catabolic activities upon tissue loss. These findings portray PTEN as a node coordinating liver growth with its energy demands and emphasize the need of lipids for regeneration. (H<jats:sc>epatology<\/jats:sc>2017;66:908\u2013921).<\/jats:p>","DOI":"10.1002\/hep.29226","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T23:43:04Z","timestamp":1493077384000},"page":"908-921","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":61,"title":["PTEN Down\u2010Regulation Promotes \u03b2\u2010Oxidation to Fuel Hypertrophic Liver Growth After Hepatectomy in Mice"],"prefix":"10.1097","volume":"66","author":[{"given":"Ekaterina","family":"Kachaylo","sequence":"first","affiliation":[{"name":"Department of Surgery,Swiss Hepato\u2010Pancreato\u2010Biliary and Transplantation Center, University Hospital Z\u00fcrich,Z\u00fcrich,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Tschuor","sequence":"additional","affiliation":[{"name":"Department of Surgery,Swiss Hepato\u2010Pancreato\u2010Biliary and Transplantation Center, University Hospital Z\u00fcrich,Z\u00fcrich,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Calo","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism,University of Geneva,Geneva,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Borgeaud","sequence":"additional","affiliation":[{"name":"Department of Surgery,Swiss Hepato\u2010Pancreato\u2010Biliary and Transplantation Center, University Hospital Z\u00fcrich,Z\u00fcrich,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Ungeth\u00fcm","sequence":"additional","affiliation":[{"name":"Department of Surgery,Swiss Hepato\u2010Pancreato\u2010Biliary and Transplantation Center, University Hospital Z\u00fcrich,Z\u00fcrich,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perparim","family":"Limani","sequence":"additional","affiliation":[{"name":"Department 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