martin-caveolin1-2013.pdf (2.6 MB)
Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling
journal contribution
posted on 2013-01-01, 00:00 authored by M Fernandez-Rojo, M Gongora, R Fitzsimmons, N Martel, Sheree MartinSheree Martin, S Nixon, A Brooks, M Ikonomopoulou, S Martin, H Lo, S Myers, C Restall, C Ferguson, P Pilch, Sean McgeeSean Mcgee, R Anderson, M Waters, J Hancock, S Grimmond, G Muscat, R PartonCaveolae 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.
History
Journal
Cell ReportsVolume
4Issue
2Pagination
238 - 247Publisher
Cell PressLocation
Cambridge, MAPublisher DOI
ISSN
2211-1247Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2013, Cell PressUsage metrics
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