{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:38:51Z","timestamp":1789205931903,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1735,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      We previously reported that mice subjected to partial hepatectomy exhibit rapid develop-ment of hypoglycemia followed by transient accumulation of fat in the early regenerating liver. We also showed that disrupting these metabolic alterations results in impaired liver regeneration. The studies reported here were undertaken to further characterize and inves-tigate the functional importance of changes in systemic adipose metabolism during normal liver regeneration. The results showed that a systemic catabolic response is induced in each of two distinct, commonly used experimental models of liver regeneration (partial hepatec-tomy and carbon tetrachloride treatment), and that this response occurs in proportion to the degree of induced hepatic insuf\ufb01ciency. Together, these observations suggest that ca-tabolism of systemic adipose stores may be essential for normal liver regeneration. To test this possibility, we investigated the hepatic regenerative response in fatty liver dystrophy (\n                      <jats:italic toggle=\"yes\">\ufb02d<\/jats:italic>\n                      ) mice, which exhibit partial lipodystrophy and have diminished peripheral adipose stores. The results showed that the development of hypoglycemia and hepatic accumula-tion of fat was attenuated and liver regeneration was impaired following partial hepatec-tomy in these animals. The\n                      <jats:italic toggle=\"yes\">\ufb02d<\/jats:italic>\n                      mice also exhibited increased hepatic p21 expression and diminished plasma levels of the adipose-derived hormones adiponectin and leptin, which have each been implicated as regulators of liver regeneration.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      These data sug-gest that the hypoglycemia that develops after partial hepatectomy induces systemic lipoly-sis followed by accumulation of fat derived from peripheral stores in the early regenerating liver, and that these events may be essential for initiation of normal liver regeneration. (HEPATOLOGY 2010;52:2109-2117)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.23920","type":"journal-article","created":{"date-parts":[[2010,8,22]],"date-time":"2010-08-22T08:09:59Z","timestamp":1282464599000},"page":"2109-2117","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":81,"title":["Liver Regeneration is Impaired in Lipodystrophic Fatty Liver Dystrophy Mice"],"prefix":"10.1097","volume":"52","author":[{"given":"Vered","family":"Gazit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Weymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hartman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian N.","family":"Finck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Hruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly","family":"Tzekov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Rudnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-26-20251124","first-page":"186","article-title":"Experimental pathology of the liver. 1. Restoration of the liver of the white rat following partial surgical removal.","volume":"12","author":"Higgins","year":"1931","journal-title":"Arch Pathol"},{"key":"R3-26-20251124","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","article-title":"Liver regeneration","volume":"276","author":"Michalopoulos","year":"1997","journal-title":"Science"},{"key":"R4-26-20251124","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0168-8278(00)80412-2","article-title":"Liver regeneration","volume":"32","author":"Fausto","year":"2000","journal-title":"J Hepatol"},{"key":"R5-26-20251124","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/jcp.21172","article-title":"Liver regeneration","volume":"213","author":"Michalopoulos","year":"2007","journal-title":"J Cell Physiol"},{"key":"R6-26-20251124","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2353\/ajpath.2010.090675","article-title":"Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas","volume":"176","author":"Michalopoulos","year":"2010","journal-title":"Am J Pathol"},{"key":"R7-26-20251124","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/0026-0495(95)90201-5","article-title":"Regulation of nutrient metabolism and energy expenditure","volume":"44","author":"Felber","year":"1995","journal-title":"Metabolism"},{"key":"R8-26-20251124","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/hep.20462","article-title":"Disruption of hepatic adipogenesis is associated with impaired liver regeneration in mice","volume":"40","author":"Shteyer","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R9-26-20251124","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/hep.22979","article-title":"p21 is required for dextrose-mediated inhibition of mouse liver regeneration","volume":"50","author":"Weymann","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R10-26-20251124","doi-asserted-by":"crossref","first-page":"8885","DOI":"10.1073\/pnas.151217998","article-title":"Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration","volume":"98","author":"Rudnick","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R11-26-20251124","doi-asserted-by":"crossref","first-page":"43107","DOI":"10.1074\/jbc.M407969200","article-title":"Delayed hepatocellular mitotic progression and impaired liver regeneration in early growth response-1-deficient mice","volume":"279","author":"Liao","year":"2004","journal-title":"J Biol Chem"},{"key":"R12-26-20251124","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1016\/j.molimm.2008.03.008","article-title":"Evidence for non-traditional activation of complement factor C3 during murine liver regeneration","volume":"45","author":"Clark","year":"2008","journal-title":"Mol Immunol"},{"key":"R13-26-20251124","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/S0016-5085(03)00270-1","article-title":"Leptin-specific mechanisms for impaired liver regeneration in ob\/ob mice after toxic injury","volume":"124","author":"Leclercq","year":"2003","journal-title":"Gastroenterology"},{"key":"R14-26-20251124","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1096\/fj.06-6511fje","article-title":"Rosiglitazone inhibits mouse liver regeneration","volume":"20","author":"Turmelle","year":"2006","journal-title":"FASEB J"},{"key":"R15-26-20251124","first-page":"1577","article-title":"Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor","volume":"152","author":"Yamada","year":"1998","journal-title":"Am J Pathol"},{"key":"R16-26-20251124","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/hep.510310123","article-title":"Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice","volume":"31","author":"Kovalovich","year":"2000","journal-title":"HEPATOLOGY"},{"key":"R17-26-20251124","doi-asserted-by":"crossref","first-page":"947","DOI":"10.2353\/ajpath.2009.090043","article-title":"Relationships between deficits in tissue mass and transcriptional programs after partial hepatectomy in mice","volume":"175","author":"Li","year":"2009","journal-title":"Am J Pathol"},{"key":"R18-26-20251124","first-page":"G905","article-title":"Control of rate and extent of the proliferative response after partial hepatectomy","volume":"273","author":"Lambotte","year":"1997","journal-title":"Am J Physiol"},{"key":"R19-26-20251124","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1126\/science.1130773","article-title":"Caveolin-1 is essential for liver regeneration","volume":"313","author":"Fernandez","year":"2006","journal-title":"Science"},{"key":"R20-26-20251124","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3109\/00365520903583848","article-title":"Propranolol impairs liver regeneration after partial hepatectomy in C57Bl6-mice by transient attenuation of hepatic lipid accumulation and increased apoptosis.","volume":"45","author":"Walldorf","year":"2010","journal-title":"Scand J Gastroenterol"},{"key":"R21-26-20251124","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/hep.22473","article-title":"Altered hepatic triglyceride content after partial hepatectomy without impaired liver regeneration in multiple murine genetic models","volume":"48","author":"Newberry","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R22-26-20251124","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/83685","article-title":"Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin","volume":"27","author":"Peterfy","year":"2001","journal-title":"Nat Genet"},{"key":"R23-26-20251124","doi-asserted-by":"crossref","first-page":"G1179","DOI":"10.1152\/ajpgi.00411.2004","article-title":"Hepatic triglyceride contents are genetically determined in mice: results of a strain survey","volume":"288","author":"Lin","year":"2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R24-26-20251124","doi-asserted-by":"crossref","first-page":"23078","DOI":"10.1074\/jbc.274.33.23078","article-title":"Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics","volume":"274","author":"Klingenspor","year":"1999","journal-title":"J Biol Chem"},{"key":"R25-26-20251124","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.diabet.2007.08.002","article-title":"Adiponectin: an update.","volume":"34","author":"Guerre-Millo","year":"2008","journal-title":"Diabetes Metab"},{"key":"R26-26-20251124","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbrc.2008.10.176","article-title":"Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice","volume":"378","author":"Ezaki","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"R27-26-20251124","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/labinvest.2009.63","article-title":"Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice","volume":"89","author":"Shu","year":"2009","journal-title":"Lab Invest"},{"key":"R28-26-20251124","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1053\/jhep.2001.28054","article-title":"Disrupted signaling and inhibited regeneration in obese mice with fatty livers: implications for nonalcoholic fatty liver disease pathophysiology","volume":"34","author":"Yang","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R29-26-20251124","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1078\/0940-2993-00265","article-title":"Impaired liver regeneration after partial hepatectomy in db\/db mice","volume":"54","author":"Yamauchi","year":"2003","journal-title":"Exp Toxicol Pathol"},{"key":"R30-26-20251124","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/labinvest.3700474","article-title":"Defective hepatic regeneration after partial hepatectomy in leptin-deficient mice is not rescued by exogenous leptin","volume":"86","author":"Leclercq","year":"2006","journal-title":"Lab Invest"},{"key":"R31-26-20251124","doi-asserted-by":"crossref","first-page":"28411","DOI":"10.1074\/jbc.M202807200","article-title":"STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration","volume":"277","author":"Li","year":"2002","journal-title":"J Biol Chem"},{"key":"R32-26-20251124","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1084\/jem.20070820","article-title":"Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3","volume":"205","author":"Riehle","year":"2008","journal-title":"J Exp Med"},{"key":"R34-26-20251124","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1073\/pnas.94.4.1441","article-title":"Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor","volume":"94","author":"Yamada","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R35-26-20251124","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/hep.510280410","article-title":"Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor","volume":"28","author":"Yamada","year":"1998","journal-title":"HEPATOLOGY"},{"key":"R36-26-20251124","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1126\/science.274.5291.1379","article-title":"Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice","volume":"274","author":"Cressman","year":"1996","journal-title":"Science"},{"key":"R37-26-20251124","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0899-9007(97)00185-8","article-title":"Cytokines and cachexia","volume":"13","author":"Matthys","year":"1997","journal-title":"Nutrition"},{"key":"R38-26-20251124","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1002\/hep.20522","article-title":"Probing Prometheus: fat fueling the fire","volume":"40","author":"Farrell","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R39-26-20251124","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.febslet.2007.11.014","article-title":"The lipin protein family: dual roles in lipid biosynthesis and gene expression","volume":"582","author":"Reue","year":"2008","journal-title":"FEBS Lett"},{"key":"R40-26-20251124","doi-asserted-by":"crossref","first-page":"G302","DOI":"10.1152\/ajpgi.00175.2002","article-title":"Impaired Ras membrane association and activation in PPARalpha knockout mice after partial hepatectomy","volume":"284","author":"Wheeler","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R41-26-20251124","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1053\/jhep.2002.35276","article-title":"Delayed liver regeneration in peroxisome proliferator-activated receptor-alpha-null mice","volume":"36","author":"Anderson","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R42-26-20251124","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cell.2009.05.036","article-title":"Identification of a physiologically relevant endogenous ligand for PPARalpha in liver","volume":"138","author":"Chakravarthy","year":"2009","journal-title":"Cell"},{"key":"R43-26-20251124","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1074\/jbc.M807882200","article-title":"Lipin 2 is a liver-enriched phosphatidate phosphohydrolase enzyme that is dynamically regulated by fasting and obesity in mice","volume":"284","author":"Gropler","year":"2009","journal-title":"J Biol Chem"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23920","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201012000-00026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T19:00:12Z","timestamp":1764010812000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201012000-00026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23920","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,12]]}}}