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 journalArticle

23 Citations (Scopus)

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 (US)
Pages (from-to)808-815
Number of pages8
JournalJournal of Lipid Research
Volume55
Issue number5
DOIs
StatePublished - May 2014

Fingerprint

Peroxisome Proliferator-Activated Receptors
Lipase
Liver
Carrier Proteins
Fatty Acids
Oxidation
Mitochondria
Hydroxybutyrates
Lipids
Gene expression
Hydrolysis
Protein Transport
Adenoviridae
Tissue
Ligands
Hepatocytes
Genotype

Keywords

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

Cite this

Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism. / Ong, Kuok Teong; Mashek, Mara T.; Davidson, Nicholas O.; Mashek, Douglas G.

In: Journal of Lipid Research, Vol. 55, No. 5, 05.2014, p. 808-815.

Research output: Contribution to journalArticle

@article{f0a0229be41a4ce8a1863b937d4ddeb2,
title = "Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism",
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.",
keywords = "Adipose triglyceride lipase, Liver fatty acid binding protein, Peroxisome proliferator-activated receptor-α, β-oxidation",
author = "Ong, {Kuok Teong} and Mashek, {Mara T.} and Davidson, {Nicholas O.} and Mashek, {Douglas G.}",
year = "2014",
month = "5",
doi = "10.1194/jlr.M039867",
language = "English (US)",
volume = "55",
pages = "808--815",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism

AU - Ong, Kuok Teong

AU - Mashek, Mara T.

AU - Davidson, Nicholas O.

AU - Mashek, Douglas G.

PY - 2014/5

Y1 - 2014/5

N2 - 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.

AB - 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.

KW - Adipose triglyceride lipase

KW - Liver fatty acid binding protein

KW - Peroxisome proliferator-activated receptor-α

KW - β-oxidation

UR - http://www.scopus.com/inward/record.url?scp=84899573610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899573610&partnerID=8YFLogxK

U2 - 10.1194/jlr.M039867

DO - 10.1194/jlr.M039867

M3 - Article

C2 - 24610891

AN - SCOPUS:84899573610

VL - 55

SP - 808

EP - 815

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 5

ER -