MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity.
MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity.
复制标题
脂肪细胞线粒体活性的线粒体驱动的改变揭示了至关重要的适应性过程，可保留肥胖症中胰岛素敏感性。
作者：
我们研究了线粒体外膜中存在的一种蛋白质--mitoNEET水平改变的啮齿动物模型。脂肪细胞特异性过表达的mitoNEET增强了脂肪的摄取和储存，导致脂肪组织块的扩张。尽管导致了大量肥胖，但脂肪组织扩张的良性方面占上风，胰岛素敏感性得到保留。MitoNEET抑制线粒体铁向基质的运输。由于铁是电子传输的限速成分，所以mitoneet可降低β氧化速率。这与线粒体膜电位降低、活性氧损伤减少以及脂联素水平升高有关。相反，mitoNEET的减少通过增加基质中的铁含量来增强线粒体的呼吸能力，从而减少高脂肪饮食下的体重增加。然而，mitoNEET的减少也会导致氧化应激和葡萄糖耐量增加。因此，mitoNEET是线粒体功能的有力调节器，它深刻地影响细胞和全身脂质动态平衡的动态。
We examined rodent models with altered levels of mitoNEET, a protein residing in the mitochondrial outer membrane. Adipocyte-specific overexpression of mitoNEET enhances lipid-uptake and storage, leading to an expansion of adipose tissue mass. Despite the resulting massive obesity, benign aspects of adipose tissue expansion prevail and insulin sensitivity is preserved. MitoNEET inhibits mitochondrial iron transport into the matrix. Since iron is a rate-limiting component for electron transport, mitoNEET reduces β-oxidation rates. This is associated with reduced mitochondrial membrane potential and reduced reactive oxygen species damage, along with higher levels of adiponectin production. Conversely, the reduction of mitoNEET enhances mitochondrial respiratory capacity through enhanced iron content in the matrix, with reduced weight gain on a high fat diet. However, a reduction of mitoNEET also causes heightened oxidative-stress and glucose-intolerance. MitoNEET is therefore a potent regulator of mitochondrial function that profoundly impacts the dynamics of cellular and whole-body lipid homeostasis.
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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：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
15.9
作者：
Bonnard, Charlotte;Durand, Annie;Rieusset, Jennifer
通讯作者：
Rieusset, Jennifer
影响因子：
4.8
作者：
Combs, TP;Pajvani, UB;Scherer, PE
通讯作者：
Scherer, PE
影响因子：
15.9
作者：
Berglund, Eric D.;Vianna, Claudia R.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.