Animal data indicate that ketogenic diets are associated with improved mitochondrial function, but human data are lacking. We aimed to characterize skeletal muscle mitochondrial changes in response to a ketogenic diet combined with exercise training in healthy individuals. Twenty-nine physically active adults completed a 12-week supervised exercise program after self-selection into a ketogenic diet (KD, n=15) group or maintenance of their habitual mixed diet (MD, n=14). Measures of metabolic health and muscle biopsies (Vastus lateralis) were obtained before and after the intervention. Mitochondria were isolated from muscle and studied after exposure to carbohydrate (pyruvate), fat (palmitoyl-L-carnitine), and ketone (β-hydroxybutyrate+acetoacetate) substrates. Compared to MD, the KD resulted in increased whole-body resting fat oxidation (p<0.001) and decreased fasting insulin (p=0.019), insulin resistance (HOMA-IR, p=0.022), and visceral fat (p<0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, p=0.009), ATP production (36%, p=0.028), and ATP/H₂O₂ (36%, p=0.033) with the fat-based substrate. ATP production with the ketone-based substrate was 4 to 8 times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, p=0.035) and an increase in muscle triglyceride (81%, p=0.006). These results expand our understanding of human adaptation to a ketogenic diet combined with exercise. In conjunction with weight loss, we observed altered skeletal muscle mitochondrial function and efficiency, an effect that may contribute to the therapeutic use of ketogenic diets in various clinical conditions, especially those associated with insulin resistance.

中文翻译：

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改善运动代谢的人体骨骼肌中的酮运动饮食与运动性兴奋剂线粒体功能。

动物数据表明，生酮饮食与改善的线粒体功能有关，但缺乏人类数据。我们旨在表征在健康个体中，对生酮饮食和运动训练相结合的骨骼肌线粒体变化。自选为生酮饮食（KD，n = 15）组或维持其习惯性混合饮食（MD，n = 14）后，有29名体育锻炼的成年人完成了为期12周的有监督运动计划。在干预之前和之后，测量代谢健康和肌肉活检（外侧大头肌）。从肌肉中分离出线粒体，并在暴露于碳水化合物（丙酮酸），脂肪（棕榈酰-L-肉碱）和酮（β-羟基丁酸酯+乙酰乙酸）底物后进行研究。与MD相比，KD导致全身静息脂肪氧化增加（p <0。001）和空腹胰岛素（p = 0.019），胰岛素抵抗（HOMA-IR，p = 0.022）和内脏脂肪减少（p <0.001）。线粒体呼吸控制率（19％，p = 0.009），ATP产生（36％，p = 0.028）和ATP / H的增加证明了KD改变了线粒体功能₂ O ₂（36％，p = 0.033）和脂肪基物质。酮基底物的ATP生成量比其他底物低4至8倍，表明氧化最少。KD导致肌肉糖原的少量减少（14％，p = 0.035）和肌肉甘油三酸酯的增加（81％，p = 0.006）。这些结果扩展了我们对人类适应生酮饮食与运动相结合的理解。伴随着体重减轻，我们观察到骨骼肌线粒体功能和效率的改变，这种作用可能有助于在各种临床情况下，特别是与胰岛素抵抗相关的生酮饮食的治疗用途。