Delayed liver regeneration after partial hepatectomy in adipose differentiation related protein-null mice

Motoyuki Kohjima, Tsung Huang Tsai, Bryan C. Tackett, Sundararajah Thevananther, Lan Li, Benny Hung Junn Chang, Lawrence Chan

研究成果: Contribution to journalArticle査読

25 被引用数 (Scopus)

抄録

Background & Aims Adult hepatocytes undergo cell cycle progression and proliferation in response to partial hepatectomy (PH). Transient lipid accumulation within hepatocytes preceding the peak proliferative phase is a characteristic feature of regenerating livers. However, the molecular mediators and mechanisms responsible for lipid accumulation in regenerating livers are not well understood. Adipose differentiation related protein (ADRP; Plin2) regulates hepatic triglyceride storage and Plin2-deficient (Plin2-/-) mice have significantly reduced triglyceride (TG) content in the liver. We sought to determine the functional significance of PLIN2 in liver regeneration in response to PH and toxic liver injury and examined whether absence of Plin2 expression modulates hepatocyte proliferation and liver regeneration. Methods We subjected wild-type (WT) and Plin2-/- mice to 70% PH or acute carbon tetrachloride (CCL4) treatment and examined the hepatic lipid content, the expression profile of lipid metabolism-related genes, the rate of cellular proliferation and the dynamics of liver regeneration in the treated animals. Results In response to PH, Plin2-/- mice showed decreased hepatic triglyceride accumulation and delayed cell cycle progression, which was associated with impaired liver regeneration. Fatty acid (FA) synthesis and lipid transfer gene expression profile were comparable between Plin2-/- and wild-type mice, while VLDL secretion rate was higher in the Plin2 -/- mice. Downregulated β-oxidation and reduced cytosolic FA level in Plin2-/- mice may have contributed to the attenuation of the liver regeneration capacity in these animals. In parallel experiments, we also observed attenuated hepatic lipid accumulation and proliferation in response to CCl4-mediated acute toxic liver injury in Plin2-/- mice. Conclusions We conclude that PLIN2-mediated lipid accumulation and utilization by the liver is important for efficient liver regeneration in response to PH and toxic liver injury.

本文言語英語
ページ(範囲)1246-1254
ページ数9
ジャーナルJournal of Hepatology
59
6
DOI
出版ステータス出版済み - 12 2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 肝臓学

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