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

被引：55

作者：

Fernandez-Rojo, Manuel A. ^{[1
]}

Gongora, Milena ^{[1
]}

Fitzsimmons, Rebecca L. ^{[1
]}

Martel, Nick ^{[1
]}

Martin, Sheree D. ^{[4
]}

Nixon, Susan J. ^{[1
]}

Brooks, Andrew J. ^{[1
]}

Ikonomopoulou, Maria P. ^{[1
]}

Martin, Sally ^{[1
]}

Lo, Harriet P. ^{[1
]}

Myers, Stephen A. ^{[1
]}

Restall, Christina ^{[5
]}

Ferguson, Charles ^{[1
,2
]}

Pilch, Paul F. ^{[8
]}

McGee, Sean L. ^{[4
]}

Anderson, Robin L. ^{[5
,6
]}

Waters, Michael J. ^{[1
]}

Hancock, John F. ^{[7
]}

Grimmond, Sean M. ^{[1
]}

Muscat, George E. O. ^{[1
,3
]}

Parton, Robert G. ^{[1
,2
]}

机构：

[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4067, Australia

[2] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld 4067, Australia

[3] Univ Queensland, Obes Res Ctr, Brisbane, Qld 4067, Australia

[4] Deakin Univ, Sch Med, Metab Res Unit, Geelong, Vic 3217, Australia

[5] Peter MacCallum Canc Inst, Melbourne, Vic 8006, Australia

[6] Univ Melbourne, Dept Pathol, Melbourne, Vic 8006, Australia

[7] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

[8] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA

来源：

CELL REPORTS | 2013年 / 4卷 / 02期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

CHAIN FATTY-ACIDS; LIVER-REGENERATION; NUCLEAR RECEPTORS; PPAR-ALPHA; MICE; EXPRESSION; GLUCOSE; LIPODYSTROPHY; HEPATOCYTES; DYSFUNCTION;

D O I：

10.1016/j.celrep.2013.06.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (PPAR alpha)-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 PPARa ligand signaling and attenuated bile acid and FXR alpha signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPAR alpha, FXR alpha, and SHP) and bile acid signaling.

引用

页码：238 / 247

页数：10

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