Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling

Manuel Alejandro Fernandez-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 Anderson, Michael J Waters, John F Hancock, Sean Grimmond, George EO MuscatRobert G Parton

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33 Citations (Scopus)

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 alpha (PPARalpha)-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 PPARalpha ligand signaling and attenuated bile acid and FXRalpha signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARalpha, FXRalpha, and SHP) and bile acid signaling.
Original languageEnglish
Pages (from-to)238 - 247
Number of pages10
JournalCell Reports
Volume4
Issue number2
DOIs
Publication statusPublished - 2013

Cite this

Fernandez-Rojo, M. A., Gongora, M., Fitzsimmons, R. L., Martel, N., Martin, S. D., Nixon, S. J., Brooks, A. J., Ikonomopoulou, M. P., Martin, S., Lo, H. P., Myers, S. A., Restall, C., Ferguson, C., Pilch, P. F., McGee, S. L., Anderson, R., Waters, M. J., Hancock, J. F., Grimmond, S., ... Parton, R. G. (2013). Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling. Cell Reports, 4(2), 238 - 247. https://doi.org/10.1016/j.celrep.2013.06.017