CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells

J. Mark Brown, Soonkyu Chung, Akash Das, Gregory S. Shelness, Lawrence L. Rudel, Liqing Yu

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Comparative Gene Identification-58 (CGI-58) is a member of the α/β-hydrolase family of proteins. Mutations in the human CGI-58 gene are associated with Chanarin-Dorfman syndrome, a rare autosomal recessive genetic disease in which excessive triglyceride (TG) accumulation occurs in multiple tissues. In this study, we investigated the role of CGI-58 in cellular lipid metabolism in several cell models and discovered a role for CGI-58 in promoting the packaging of cytoplasmic TG into secreted lipoprotein particles in hepatoma cells. Using both gain-of-function and loss-of-function approaches, we demonstrate that CGI-58 facilitates the depletion of cellular TG stores without altering cellular cholesterol or phospholipid accumulation. This depletion of cellular TG is attributable solely to augmented hydrolysis, whereas TG synthesis was not affected by CGI-58. Furthermore, CGI-58-mediated TG hydrolysis can be completely inhibited by the known lipase inhibitors diethylumbelliferyl phosphate and diethyl-p-nitrophenyl phosphate, but not by p-chloro- mercuribenzoate. Intriguingly, CGI-58-driven TG hydrolysis was coupled to increases in both fatty acid oxidation and secretion of TG. Collectively, this study reveals a role for CGI-58 in coupling lipolytic degradation of cytoplasmic TG to oxidation and packaging into TG-rich lipoproteins for secretion in hepatoma cells.

Original languageEnglish (US)
Pages (from-to)2295-2305
Number of pages11
JournalJournal of Lipid Research
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2007

Keywords

  • Comparative Gene Identification-58
  • Lipolysis
  • Triglyceride hydrolysis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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