Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

• DOI: 10.1016/j.celrep.2013.06.017
• Publication Date: 2013-07-11T15:30:28Z
• Authors: Manuel A. Fernánd...; Milena Gongora; Rebecca L. Fitzsi...; Nick Martel; Sheree D. Martin; Susan J. Nixon; Andrew J. Brooks; Maria P. Ikonomop...; 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
• Keywords: Crosstalk; Caveolin; Caveolin 1; Oxidative metabolism

Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues vivo is lacking. Unbiased expression profiling 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 ketogenesis. Similar results were recapitulated CAV1-deficient AML12 hepatocytes, suggesting at least partial cell-autonomous role of hepatocyte metabolic adaptation fasting. Finally, our experiments suggest that phenotypes observed involve PPARα ligand signaling attenuated bile FXRα signaling. These demonstrate significance (1) homeostasis (2) nuclear hormone (PPARα, FXRα, SHP)