OSU Interdisciplinary PhD Program in Nutrition, Department of Human Sciences, The Ohio State University, Columbus, Ohio.
Department of Human Sciences, The Ohio State University, Columbus, Ohio.
Am J Physiol Endocrinol Metab. 2020 Dec 1;319(6):E995-E1007. doi: 10.1152/ajpendo.00305.2020. Epub 2020 Sep 28.
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-wk supervised exercise program after self-selection into a ketogenic diet (KD, = 15) group or maintenance of their habitual mixed diet (MD, = 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 with MD, the KD resulted in increased whole body resting fat oxidation ( < 0.001) and decreased fasting insulin ( = 0.019), insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), = 0.022], and visceral fat ( < 0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, = 0.009), ATP production (36%, = 0.028), and ATP/HO (36%, = 0.033) with the fat-based substrate. ATP production with the ketone-based substrate was four to eight times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, = 0.035) and an increase in muscle triglyceride (81%, = 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.
动物数据表明，生酮饮食与改善线粒体功能有关，但人类数据缺乏。我们旨在描述健康个体中酮饮食结合运动训练对骨骼肌线粒体变化的影响。29 名有运动习惯的成年人在自主选择生酮饮食（KD，n=15）或维持混合饮食（MD，n=14）后，完成了 12 周的监督运动计划。干预前后测量代谢健康和肌肉活检（股外侧肌）。将肌肉分离的线粒体暴露于碳水化合物（丙酮酸）、脂肪（棕榈酰肉碱）和酮体（β-羟丁酸+乙酰乙酸）底物后进行研究。与 MD 相比，KD 导致静息状态下全身脂肪氧化增加（<0.001），空腹胰岛素降低（=0.019），胰岛素抵抗增加[稳态模型评估的胰岛素抵抗（HOMA-IR），=0.022]，内脏脂肪减少（<0.001）。KD 改变了线粒体功能，表现为线粒体呼吸控制比（增加 19%，=0.009）、ATP 生成（增加 36%，=0.028）和 ATP/HO（增加 36%，=0.033）增加，而基于脂肪的底物。基于酮的底物的 ATP 生成比其他底物低四到八倍，表明氧化程度低。KD 导致肌肉糖原减少 14%（=0.035），肌肉甘油三酯增加 81%（=0.006）。这些结果扩展了我们对人类适应生酮饮食结合运动的理解。与体重减轻相结合，我们观察到骨骼肌线粒体功能和效率的改变，这种效应可能有助于在各种临床情况下使用生酮饮食，特别是在与胰岛素抵抗相关的情况下。
