title: Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling.
abstract: Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1-/- mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Fernández-Rojo
authors.forename: Milena
authors.initials: M
authors.lastname: Gongora
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Fitzsimmons
authors.forename: Nick
authors.initials: N
authors.lastname: Martel
authors.forename: Sheree D
authors.initials: SD
authors.lastname: Martin
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Nixon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brooks
authors.forename: Maria P
authors.initials: MP
authors.lastname: Ikonomopoulou
authors.forename: Sally
authors.initials: S
authors.lastname: Martin
authors.forename: Harriet P
authors.initials: HP
authors.lastname: Lo
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Myers
authors.forename: Christina
authors.initials: C
authors.lastname: Restall
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pilch
authors.forename: Sean L
authors.initials: SL
authors.lastname: McGee
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Waters
authors.forename: John F
authors.initials: JF
authors.lastname: Hancock
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: George E O
authors.initials: GE
authors.lastname: Muscat
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts; D051242:Caveolin 1