Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle
Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle
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DOI：
10.1152/ajpendo.00410.2020
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发表时间：
2021-06-01
影响因子：
5.1
通讯作者：
Noland, Robert C.
中科院分区：
文献类型：
--
作者：
Huang, Tai-Yu;Linden, Melissa A.;Noland, Robert C.
据报道，生酮饮食（KD）可以改善人类的体重、脂肪量和运动表现。不幸的是，大多数啮齿动物研究都使用低蛋白KD，这并不能概括人类使用的饮食。由于骨骼肌在应对饮食和运动引起的大量营养素扰动中起着关键作用，因此本研究的目的是测试正常蛋白KD（NPKD）是否会影响骨骼肌底物氧化能力在运动训练（ExTr）中的变化。C57 BL/6 J雄性小鼠连续6周给予高脂肪、碳水化合物缺乏的NPKD（16.1%蛋白质、83.9%脂肪、0%碳水化合物），而对照组（Con）给予含相似蛋白质（15.9%蛋白质、11.9%脂肪、72.2%碳水化合物）的低脂饮食。饮食3周后，小鼠开始跑步机训练5天/周，60分钟/天，持续3 wkNPKD增加体重和脂肪量，而ExTr否定了肥胖的持续上升。ExTr增加肌内糖原，而NPKD增加肌内甘油三酯。NPKD和ExTr单独都没有改变线粒体含量;然而，在组合中，NPKD-ExTr组显示PGC-1a和线粒体分裂/融合标志物增加。丙酮酸氧化能力没有变化的干预，而ExTr增加亮氨酸氧化NPKD喂养的小鼠。脂质代谢途径有最显着的变化，因为NPKD和ExTr干预都增强了线粒体和过氧化物酶体的脂质氧化，许多适应是相加或协同的。总的来说，这些结果表明，NPKD和ExTr的组合诱导骨骼肌氧化能力的加性和/或协同适应。新&值得注意的是正常蛋白质含量的生酮饮食（NPKD）增加体重和脂肪量，增加肌内甘油三酯储存，并上调与蛋白质代谢相关的途径。与运动训练组合，NPKD诱导骨骼肌中AMPK、PGC-1a、线粒体分裂/融合基因、线粒体脂肪酸氧化和过氧化物酶体适应的加和/或协同激活。总的来说，这项研究的结果提供了骨骼肌适应机制的见解与酮适应。
Ketogenic diets (KDs) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). A high fat, carbohydrate-deficient NPKD (16.1% protein, 83.9% fat, 0% carbohydrate) was given to C57BL/6J male mice for 6 wk, whereas controls (Con) received a low-fat diet with similar protein (15.9% protein, 11.9% fat, 72.2% carbohydrate). After 3 wk on the diet, mice began treadmill training 5 days/wk, 60 min/day for 3 wks. The NPKD increased body weight and fat mass, whereas ExTr negated a continued rise in adiposity. ExTr increased intramuscular glycogen, whereas the NPKD increased intramuscular triglycerides. Neither the NPKD nor ExTr alone altered mitochondrial content; however, in combination, the NPKD-ExTr group showed increases in PGC-1a and markers of mitochondrial fission/fusion. Pyruvate oxidative capacity was unchanged by either intervention, whereas ExTr increased leucine oxidation in NPKD-fed mice. Lipid metabolism pathways had the most notable changes as the NPKD and ExTr interventions both enhanced mitochondrial and peroxisomal lipid oxidation and many adaptations were additive or synergistic. Overall, these results suggest that a combination of a NPKD and ExTr induces additive and/or synergistic adaptations in skeletal muscle oxidative capacity.NEW & NOTEWORTHY A ketogenic diet with normal protein content (NPKD) increases body weight and fat mass, increases intramuscular triglyceride storage, and upregulates pathways related to protein metabolism. In combination with exercise training, a NPKD induces additive and/or synergistic activation of AMPK, PGC-1a, mitochondrial fission/fusion genes, mitochondrial fatty acid oxidation, and peroxisomal adaptations in skeletal muscle. Collectively, results from this study provide mechanistic insight into adaptations in skeletal muscle relevant to keto-adaptation.