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Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL).

Publication ,  Journal Article
Chung, C; Doll, JA; Gattu, AK; Shugrue, C; Cornwell, M; Fitchev, P; Crawford, SE
Published in: J Hepatol
March 2008

BACKGROUND/AIMS: Anti-angiogenic pigment epithelium-derived factor (PEDF) is a 50 kDa secreted glycoprotein that is highly expressed in hepatocytes. Adipose triglyceride lipase (ATGL), a novel lipase critical for triglyceride metabolism, is a receptor for PEDF. We postulated that hepatocyte triglyceride metabolism was dependent on interactions between PEDF and ATGL, and loss of PEDF would impair mobilization of triglycerides in the liver. METHODS: Immunoprecipitation studies were performed in PEDF null and control hepatocytes with recombinant PEDF (rPEDF) as bait. Immunofluorescent microscopy was used to localize ATGL. Triglyceride content was analyzed in hepatocytes and in whole liver with and without rPEDF. ATGL was blocked using an inhibitor, (R)-bromoenol lactone. RESULTS: PEDF co-immunoprecipitated with ATGL in hepatic and HCC lysates. All PEDF deficient livers demonstrated steatosis. Triglyceride content was significantly increased in PEDF null livers compared to wildtype (p<0.05) and in isolated hepatocytes (p<0.01). Treatment of PEDF null hepatocytes with rPEDF decreased TG content (p<0.05) and this activity was dependent on ATGL. CONCLUSIONS: Our results identify a novel role for PEDF in hepatic triglyceride homeostasis through binding to ATGL and demonstrate that rPEDF and ATGL localize to adiposomes in hepatocytes. Dysregulation of this pathway may be one mechanism underlying fatty liver disease.

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Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

March 2008

Volume

48

Issue

3

Start / End Page

471 / 478

Location

Netherlands

Related Subject Headings

  • Triglycerides
  • Serpins
  • Recombinant Proteins
  • Pyrones
  • Phosphodiesterase Inhibitors
  • Nerve Growth Factors
  • Naphthalenes
  • Mice, Knockout
  • Mice
  • Liver
 

Citation

APA
Chicago
ICMJE
MLA
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Chung, C., Doll, J. A., Gattu, A. K., Shugrue, C., Cornwell, M., Fitchev, P., & Crawford, S. E. (2008). Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL). J Hepatol, 48(3), 471–478. https://doi.org/10.1016/j.jhep.2007.10.012
Chung, Chuhan, Jennifer A. Doll, Arijeet K. Gattu, Christine Shugrue, Mona Cornwell, Philip Fitchev, and Susan E. Crawford. “Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL).J Hepatol 48, no. 3 (March 2008): 471–78. https://doi.org/10.1016/j.jhep.2007.10.012.
Chung C, Doll JA, Gattu AK, Shugrue C, Cornwell M, Fitchev P, et al. Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL). J Hepatol. 2008 Mar;48(3):471–8.
Chung, Chuhan, et al. “Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL).J Hepatol, vol. 48, no. 3, Mar. 2008, pp. 471–78. Pubmed, doi:10.1016/j.jhep.2007.10.012.
Chung C, Doll JA, Gattu AK, Shugrue C, Cornwell M, Fitchev P, Crawford SE. Anti-angiogenic pigment epithelium-derived factor regulates hepatocyte triglyceride content through adipose triglyceride lipase (ATGL). J Hepatol. 2008 Mar;48(3):471–478.
Journal cover image

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

March 2008

Volume

48

Issue

3

Start / End Page

471 / 478

Location

Netherlands

Related Subject Headings

  • Triglycerides
  • Serpins
  • Recombinant Proteins
  • Pyrones
  • Phosphodiesterase Inhibitors
  • Nerve Growth Factors
  • Naphthalenes
  • Mice, Knockout
  • Mice
  • Liver