Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1.
Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1.
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DOI：
10.1016/j.cmet.2012.01.004
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发表时间：
2012-02-08
期刊：
影响因子：
29
通讯作者：
Scherer PE
中科院分区：
文献类型：
--
作者：
Asterholm IW;Mundy DI;Weng J;Anderson RG;Scherer PE
小窝蛋白-1是质膜内筏结构的主要结构组分，并且已经被认为是细胞信号转导的调节剂，在脂肪细胞中显著表达。在这里，我们开始全面表征小窝蛋白-1基因敲除小鼠中失调的代谢途径。我们发现，这些小鼠显示出循环中总脂联素和高分子量脂联素水平的降低，以及对进食/禁食条件的反应中改变底物使用的能力的降低。Caveolin-1缺失小鼠非常瘦，但尽管脂肪营养不良和大量代谢功能障碍，但仍保留肌肉质量。肝纤维化的发生是慢性的，而肝脂肪变性是减少。我们的数据表明，小窝蛋白-1基因敲除小鼠的复杂表型是由脂肪组织中代谢和线粒体功能的改变引起的，随后的代偿反应主要由肝脏驱动。该小鼠模型强调了脂肪组织对全系统保持代谢灵活性的核心贡献。
Caveolin-1 is a major structural component of raft structures within the plasma membrane and has been implicated as a regulator of cellular signal transduction with prominent expression in adipocytes. Here, we embarked on a comprehensive characterization of the metabolic pathways dysregulated in caveolin-1 null mice. We found that these mice display decreased circulating levels of total and high molecular weight adiponectin and a reduced ability to change substrate use in response to feeding/fasting conditions. Caveolin-1 null mice are extremely lean, but retain muscle mass despite lipodystrophy and massive metabolic dysfunction. Hepatic gluconeogenesis is chronically elevated, while hepatic steatosis is reduced. Our data suggest that the complex phenotype of the caveolin-1 null mouse is caused by altered metabolic and mitochondrial function in adipose tissue with a subsequent compensatory response driven mostly by the liver. This mouse model highlights the central contributions of adipose tissue for system-wide preservation of metabolic flexibility.
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影响因子：
7.7
作者：
Curtis JM;Grimsrud PA;Wright WS;Xu X;Foncea RE;Graham DW;Brestoff JR;Wiczer BM;Ilkayeva O;Cianflone K;Muoio DE;Arriaga EA;Bernlohr DA
通讯作者：
Bernlohr DA
影响因子：
9.2
作者：
Bosch, Marta;Mari, Montserrat;Herms, Albert;Fernandez, Ana;Fajardo, Alba;Kassan, Adam;Giralt, Albert;Colell, Anna;Balgoma, David;Barbero, Elisabet;Gonzalez-Moreno, Elena;Matias, Nuria;Tebar, Francesc;Balsinde, Jesus;Camps, Marta;Enrich, Carlos;Gross, Steven P.;Garcia-Ruiz, Carmen;Perez-Navarro, Esther;Fernandez-Checa, Jose C.;Pol, Albert
通讯作者：
Pol, Albert
DOI：
10.1007/s11626-008-9168-z
发表时间：
2009-05-01
影响因子：
2.1
作者：
Babich, H.;Liebling, E. J.;Schuck, A. G.
通讯作者：
Schuck, A. G.
DOI：
10.1073/pnas.79.2.315
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
ELMAGHRABI, MR;CLAUS, TH;PILKIS, SJ
通讯作者：
PILKIS, SJ
影响因子：
4.8
作者：
Combs, TP;Pajvani, UB;Scherer, PE
通讯作者：
Scherer, PE