Cited by 235Liver physiology and pathologyLiver Disease Diagnosis and TreatmentTissue Engineering and Regenerative Medicine

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Disruption of Hepatic Adipogenesis Is Associated With Impaired Liver Regeneration in Mice

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Shteyer, Eyal, Liao, Yunjun, Muglia, Louis J., Hruz, Paul W., Rudnick, David A.·2004·Hepatology

DOI 10.1002/hep.20462

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Abstract

The liver responds to injury with regulated tissue regeneration. During early regeneration, the liver accumulates fat. Neither the mechanisms responsible for nor the functional significance of this transient steatosis have been determined. In this study, we examined patterns of gene expression associated with hepatic fat accumulation in regenerating liver and tested the hypothesis that disruption of hepatic fat accumulation would be associated with impaired hepatic regeneration. First, microarray–based gene expression analysis revealed that several genes typically induced during adipocyte differentiation were specifically upregulated in the regenerating liver prior to peak hepatocellular fat accumulation. These observations suggest that hepatic fat accumulation is specifically regulated during liver regeneration. Next, 2 methods were employed to disrupt hepatocellular fat accumulation in the regenerating liver. Because exogenous leptin supplementation reverses hepatic steatosis in leptin–deficient mice, the effects of leptin supplementation on liver regeneration in wild–type mice were examined. The data showed that leptin supplementation resulted in suppression of hepatocellular fat accumulation and impairment of hepatocellular proliferation during liver regeneration. Second, because glucocorticoids regulate cellular fat accumulation during adipocyte differentiation, the effects of hepatocyte–specific disruption of the glucocorticoid receptor were similarly evaluated. The results showed that hepatic fat accumulation and hepatocellular proliferation were also suppressed in mice with liver specific disruption of glucocorticoid receptor. In conclusion , suppression of hepatocellular fat accumulation is associated with impaired hepatocellular proliferation following partial hepatectomy, indicating that hepatocellular fat accumulation is specifically regulated during and may be essential for normal liver regeneration. (Hepatology 2004;40:1322-1332.)

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Authors: Shteyer, E., Liao, Y., Muglia, L. J., Hruz, P. W., & Rudnick, D. A.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Rudnick, David A.
ORCID: Shteyer, Eyal
Liao, Yunjun
Muglia, Louis J.
Hruz, Paul W.
Rudnick, David A.
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2004-12
Volume: 40
Issue: 6
Pages: 1322-1332
ISSN: 0270-9139 (ISSN-L)
DOI: 10.1002/hep.20462
OpenAlex: W2013853905
Cited by: 234
References: 53
Citations by year: 2026: 8 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 13 · 2019: 9 · 2018: 14 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 4 · 2013: 14 · 2012: 18
FWCI: 5.61
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3926 d)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
Funders: Alvin J. Siteman Cancer Center
National Institutes of Health (1p30hd033688-01, 1r03dk064653-01, DK064572)
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-52574, DK-02900, DK64653, R01DK064572, DK-064572, K08DK002900, P30DK052574)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33688)
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords: liver regeneration, hepatic steatosis, leptin, glucocorticoid receptor, hepatocyte proliferation, partial hepatectomy, gene expression, ob/ob mice
MeSH terms: Animals, Cell Division, Fats, Hepatectomy, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Receptors, Glucocorticoid, Oligonucleotide Array Sequence Analysis, Leptin, Hepatocytes, Mice

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Disruption of Hepatic Adipogenesis Is Associated With Impaired Liver Regeneration in Mice

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