Endothelial nitric oxide synthase (eNOS) knockout mice have defective mitochondrial β-oxidation
Endothelial nitric oxide synthase (eNOS) knockout mice have defective mitochondrial β-oxidation
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DOI：
10.2337/db06-1228
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发表时间：
2007-11-01
期刊：
影响因子：
7.7
通讯作者：
Vollenweider, Peter
中科院分区：
文献类型：
--
作者：
Le Gouill, Eric;Jimenez, Maria;Vollenweider, Peter
最近的观察表明，内皮型一氧化氮合酶（eNOS）提供的一氧化氮不仅对代谢稳态至关重要，而且对线粒体生物合成也很重要，线粒体是游离脂肪酸（FFA）氧化和能量产生的关键细胞器。因为缺乏eNOS基因的小鼠（eNOS（-/-））除了高血压和胰岛素抵抗外，还增加了甘油三酯和FFA水平，研究设计和方法-在C57 BL/6 J野生型或eNOS（-/-）中评估线粒体活性的几个标志物，通过间接量热法测定小鼠的能量消耗和氧消耗，从骨骼肌分离的线粒体中的体外β-氧化，以及脂肪酸氧化相关基因的表达。（-10%，P < 0.05）和耗氧量（-15%，P < 0.05）。这与线粒体含量减少约30%（P < 0.05）有关，最重要的是，与线粒体功能障碍有关，如骨骼肌中肌膜下线粒体的β-氧化显著降低（-30%，P < 0.05）所证明的。最后，受损的线粒体β-氧化与腓肠肌肌细胞内脂质含量（30%，P < 0.05）的显着增加。结论-这些数据表明，升高的FFA和甘油三酯eNOS（-/-）小鼠导致缺陷的线粒体β-氧化在肌细胞。
OBJECTIVE-Recent observations indicate that the delivery of nitric oxide by endothelial nitric oxide synthase (eNOS) is not only critical for metabolic homeostasis, but could also be important for mitochondrial biogenesis, a key organelle for free fatty acid (FFA) oxidation and energy production. Because mice deficient for the gene of eNOS (eNOS(-/-)) have increased tri-glycerides and FFA levels, in addition to hypertension and insulin resistance, we hypothesized that these knockout mice may have decreased energy expenditure and defective beta-oxidation.RESEARCH DESIGN AND METHODS-Several markers of mitochondrial activity were assessed in C57BL/6J wild-type or eNOS(-/-) mice including the energy expenditure and oxygen consumption by indirect calorimetry, in vitro beta-oxidation in isolated mitochondria from skeletal muscle, and expression of genes involved in fatty acid oxidation.RESULTS-eNOS(-/-) mice had markedly lower energy expenditure (- 10%, P < 0.05) and oxygen consumption (-15%, P < 0.05) than control mice. This was associated with a roughly 30% decrease of the mitochondria content (P < 0.05) and, most importantly, with mitochondrial dysfunction, as evidenced by a markedly lower beta-oxidation of subsarcolemmal mitochondria in skeletal muscle (-30%, P < 0.05). Finally, impaired mitochondrial beta-oxidation was associated with a significant increase of the intramyocellular lipid content (30%, P < 0.05) in gastrocnemius muscle.CONCLUSIONS-These data indicate that elevated FFA and triglyceride in eNOS(-/-) mice result in defective mitochondrial beta-oxidation in muscle cells.