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 Muscat; Robert G Parton

doi:10.1016/j.celrep.2013.06.017

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

54 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 language	English
Pages (from-to)	238 - 247
Number of pages	10
Journal	Cell Reports
Volume	4
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2013.06.017
Publication status	Published - 2013

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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

@article{2905e362fc584c6c88f7fc00dc14e0bf,

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 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.",

author = "Fernandez-Rojo, {Manuel Alejandro} and Milena Gongora and Fitzsimmons, {Rebecca L} and Nick Martel and Martin, {Sheree D} and Nixon, {Susan J} and Brooks, {Andrew J} and Ikonomopoulou, {Maria P} and Sally Martin and Lo, {Harriet P} and Myers, {Stephen A} and Christina Restall and Charles Ferguson and Pilch, {Paul F} and McGee, {Sean L} and Robin Anderson and Waters, {Michael J} and Hancock, {John F} and Sean Grimmond and Muscat, {George EO} and Parton, {Robert G}",

year = "2013",

doi = "10.1016/j.celrep.2013.06.017",

language = "English",

volume = "4",

pages = "238 -- 247",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Elsevier",

number = "2",

}

Fernandez-Rojo, MA, Gongora, M, Fitzsimmons, RL, Martel, N, Martin, SD, Nixon, SJ, Brooks, AJ, Ikonomopoulou, MP, Martin, S, Lo, HP, Myers, SA, Restall, C, Ferguson, C, Pilch, PF, McGee, SL, Anderson, R, Waters, MJ, Hancock, JF, Grimmond, S, Muscat, GEO & Parton, RG 2013, 'Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling', Cell Reports, vol. 4, no. 2, pp. 238 - 247. https://doi.org/10.1016/j.celrep.2013.06.017

TY - JOUR

T1 - Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling

AU - Fernandez-Rojo, Manuel Alejandro

AU - Gongora, Milena

AU - Fitzsimmons, Rebecca L

AU - Martel, Nick

AU - Martin, Sheree D

AU - Nixon, Susan J

AU - Brooks, Andrew J

AU - Ikonomopoulou, Maria P

AU - Martin, Sally

AU - Lo, Harriet P

AU - Myers, Stephen A

AU - Restall, Christina

AU - Ferguson, Charles

AU - Pilch, Paul F

AU - McGee, Sean L

AU - Anderson, Robin

AU - Waters, Michael J

AU - Hancock, John F

AU - Grimmond, Sean

AU - Muscat, George EO

AU - Parton, Robert G

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/23850288

U2 - 10.1016/j.celrep.2013.06.017

DO - 10.1016/j.celrep.2013.06.017

M3 - Article

SN - 2211-1247

VL - 4

SP - 238

EP - 247

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -

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

Abstract

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