Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling
Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling
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DOI：
10.1016/j.celrep.2013.06.017
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发表时间：
2013-07-01
期刊：
影响因子：
8.8
通讯作者：
Parton, Robert G.
中科院分区：
文献类型：
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作者：
Fernandez-Rojo, Manuel A.;Gongora, Milena;Parton, Robert G.
Caveolae和Caveolin-1（CAV 1）与多种细胞功能有关。然而，一个模型来解释它们在体内哺乳动物组织中的作用是缺乏的。在几种组织和细胞类型中的无偏表达谱确定脂质代谢为受CAV 1缺陷影响的主要靶点。CAV 1-/-小鼠表现出肝脏过氧化物酶体增殖物激活受体α（PPAR α）依赖性氧化脂肪酸代谢和生酮受损。在CAV 1缺陷型AML 12肝细胞中也重现了类似的结果，表明肝细胞CAV 1在对禁食的代谢适应中至少具有部分细胞自主作用。最后，我们的实验表明，在CAV 1-/-小鼠中观察到的肝脏表型涉及受损的PPARa配体信号传导和减弱的胆汁酸和FXR α信号传导。这些结果证明了CAV 1在（1）肝脏脂质稳态和（2）核激素受体（PPAR α、FXR α和SHP）和胆汁酸信号传导中的重要性。
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.