Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

Kuok Teong Ong, Mara T. Mashek, Nicholas O. Davidson, Douglas G. Mashek

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Adipose TG lipase (ATGL) catalyzes the rate-limiting step in TG hydrolysis in most tissues. We have shown that hepatic ATGL preferentially channels hydrolyzed FAs to β - oxidation and induces PPAR-α signaling. Previous studies have suggested that liver FA binding protein (L-FABP) transports FAs from lipid droplets to the nucleus for ligand delivery and to the mitochondria for β-oxidation. To determine if L-FABP is involved in ATGL-mediated FA channeling, we used adenovirus-mediated suppression or overexpression of hepatic ATGL in either WT or L-FABP KO mice. Hepatic ATGL knockdown increased liver weight and TG content of overnight fasted mice regardless of genotype. L-FABP deletion did not impair the effects of ATGL overexpression on the oxidation of hydrolyzed FAs in primary hepatocyte cultures or on serum β -hydroxybutyrate concentrations in vivo. Moreover, L-FABP deletion did not influence the effects of ATGL knockdown or overexpression on PPAR-α target gene expression. Taken together, we conclude that L-FABP is not required to channel ATGL-hydrolyzed FAs to mitochondria for β-oxidation or the nucleus for PPAR-α regulation. - Ong, K. T., M. T. Mashek, N. O. Davidson, and D. G. Mashek. Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism. J. Lipid Res. 2014. 55: 808-815.

Original languageEnglish
Pages (from-to)808-815
Number of pages8
JournalJournal of lipid research
Volume55
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Adipose triglyceride lipase
  • Liver fatty acid binding protein
  • Peroxisome proliferator-activated receptor-α
  • β-oxidation

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