Nutrient excess increases skeletal muscle oxidant production and mitochondrial fragmentation that may result in impaired mitochondrial function, a hallmark of skeletal muscle insulin resistance. This led us to explore whether an endogenous gas molecule, carbon monoxide (CO), which is thought to prevent weight gain and metabolic dysfunction in mice consuming high-fat diets, alters mitochondrial morphology and respiration in C2C12 myoblasts exposed to high-glucose (15.6 mM) and high-fat (250 µM BSA-palmitate) (HGHF). Also, skeletal muscle mitochondrial morphology, distribution, respiration and energy expenditure were examined in obese resistant (OR), and obese prone (OP) rats that consumed a high-fat and high-sucrose diet for 10-weeks with or without intermittent low-dose inhaled CO and/or exercise training. In cells exposed to HGHF, superoxide production, mitochondrial membrane potential (ΔΨm), mitochondrial fission regulatory protein dynamin related protein 1 (Drp1) and mitochondrial fragmentation increased, while mitochondrial respiratory capacity was reduced. CO decreased HGHF-induced superoxide production, Drp1 protein levels and mitochondrial fragmentation, maintained ΔΨm, and increased mitochondrial respiratory capacity. In comparison with lean OR rats, OP rats had smaller skeletal muscle mitochondria that contained disorganized cristae, a normal mitochondrial distribution but reduced citrate synthase protein expression, normal respiratory responses, and a lower energy expenditure. The combination of inhaled CO and exercise produced the greatest effect on mitochondrial morphology, increasing ADP stimulated respiration in the presence of pyruvate, and preventing a decline in resting energy expenditure. These data support a therapeutic role for CO and exercise in preserving mitochondrial morphology and respiration during metabolic overload.

中文翻译：

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一氧化碳可防止骨骼肌线粒体破碎和营养物质超负荷造成的生物能受损。

营养过剩会增加骨骼肌氧化剂的产生和线粒体破碎，这可能导致线粒体功能受损，这是骨骼肌胰岛素抵抗的标志。这促使我们探索一种内源性气体分子一氧化碳（CO）是否被认为可以防止食用高脂饮食的小鼠的体重增加和代谢功能障碍，从而改变暴露于高葡萄糖的C2C12成肌细胞的线粒体形态和呼吸（15.6） mM）和高脂（250 µM BSA-棕榈酸酯）（HGHF）。此外，还对肥胖抵抗力（OR）和肥胖高脂（OP）大鼠进食了10周高脂高蔗糖饮食而有或没有间歇性低脂饮食的骨骼肌线粒体形态，分布，呼吸和能量消耗进行了检查。吸入一氧化碳和/或运动训练。在暴露于HGHF的细胞中，超氧化物的产生，线粒体膜电位（ΔΨm），线粒体裂变调节蛋白，动力蛋白相关蛋白1（Drp1）和线粒体碎片增多，而线粒体呼吸能力降低。CO可降低HGHF诱导的超氧化物生成，Drp1蛋白水平和线粒体片段化，维持ΔΨm并增加线粒体呼吸能力。与瘦型OR大鼠相比，OP大鼠的骨骼肌线粒体更小，其杂乱无章，线粒体分布正常，但柠檬酸合酶蛋白表达降低，呼吸系统反应正常，能量消耗较低。吸入一氧化碳和运动相结合对线粒体形态产生最大影响，在丙酮酸存在下增加ADP刺激的呼吸，并防止静态能量消耗的下降。这些数据支持CO和运动在代谢超负荷过程中保持线粒体形态和呼吸的治疗作用。