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.
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN.
authors.forename: Kuok Teong
authors.initials: KT
authors.lastname: Ong
authors.forename: Mara T
authors.initials: MT
authors.lastname: Mashek
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mashek
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005215:Fasting; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D020155:3-Hydroxybutyric Acid; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008049:Lipase; D047493:PPAR alpha; D034741:RNA, Small Interfering; D014280:Triglycerides; C493320:Fabp1 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: adipose triglyceride lipase; liver fatty acid binding protein; peroxisome proliferator-activated receptor-α; β-oxidation