Cell Reports
(Jul 2013)
Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling
Manuel A. Fernández-Rojo,
Milena Gongora,
Rebecca L. Fitzsimmons,
Nick Martel,
Sheree D. Martin,
Susan J. Nixon,
Andrew J. Brooks,
Maria P. Ikonomopoulou,
Sally Martin,
Harriet P. Lo,
Stephen A. Myers,
Christina Restall,
Charles Ferguson,
Paul F. Pilch,
Sean L. McGee,
Robin L. Anderson,
Michael J. Waters,
John F. Hancock,
Sean M. Grimmond,
George E.O. Muscat,
Robert G. Parton
Affiliations
Manuel A. Fernández-Rojo
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Milena Gongora
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Rebecca L. Fitzsimmons
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Nick Martel
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Sheree D. Martin
Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria 3217, Australia
Susan J. Nixon
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Andrew J. Brooks
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Maria P. Ikonomopoulou
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Sally Martin
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Harriet P. Lo
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Stephen A. Myers
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Christina Restall
Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
Charles Ferguson
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Paul F. Pilch
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
Sean L. McGee
Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria 3217, Australia
Robin L. Anderson
Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
Michael J. Waters
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
John F. Hancock
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA
Sean M. Grimmond
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
George E.O. Muscat
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
Robert G. Parton
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia
DOI
https://doi.org/10.1016/j.celrep.2013.06.017
Journal volume & issue
Vol. 4,
no. 2
Abstract
Read online
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.
WeChat QR code
Close
