Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA.
Cell Biology and Bioimaging Core, Pennington Biomedical Research Center, Baton Rouge, LA.
Med Sci Sports Exerc. 2020 Jan;52(1):37-48. doi: 10.1249/MSS.0000000000002105.
Studies suggest ketogenic diets (KD) produce favorable outcomes (health and exercise performance); however, most rodent studies have used a low-protein KD, which does not reflect the normal- to high-protein KD used by humans. Liver has an important role in ketoadaptation due to its involvement in gluconeogenesis and ketogenesis. This study was designed to test the hypothesis that exercise training (ExTr) while consuming a normal-protein KD (NPKD) would induce additive/synergistic responses in liver metabolic pathways.
Lean, healthy male C57BL/6J mice were fed a low-fat control diet (15.9% kcal protein, 11.9% kcal fat, 72.2% kcal carbohydrate) or carbohydrate-deficient NPKD (16.1% protein, 83.9% kcal fat) for 6 wk. After 3 wk on the diet, half were subjected to 3-wk treadmill ExTr (5 d·wk, 60 min·d, moderate-vigorous intensity). Upon conclusion, metabolic and endocrine outcomes related to substrate metabolism were tested in liver and pancreas.
NPKD-fed mice had higher circulating β-hydroxybutyrate and maintained glucose at rest and during exercise. Liver of NPKD-fed mice had lower pyruvate utilization and greater ketogenic potential as evidenced by higher oxidative rates to catabolize lipids (mitochondrial and peroxisomal) and ketogenic amino acids (leucine). ExTr had higher expression of the gluconeogenic gene, Pck1, but lower hepatic glycogen, pyruvate oxidation, incomplete fat oxidation, and total pancreas area. Interaction effects between the NPKD and ExTr were observed for intrahepatic triglycerides, as well as genes involved in gluconeogenesis, ketogenesis, mitochondrial fat oxidation, and peroxisomal markers; however, none were additive/synergistic. Rather, in each instance the interaction effects showed the NPKD and ExTr opposed each other.
An NPKD and an ExTr independently induce shifts in hepatic metabolic pathways, but changes do not seem to be additive/synergistic in healthy mice.
研究表明生酮饮食（KD）可产生有利的结果（健康和运动表现）；然而，大多数啮齿动物研究都使用了低蛋白 KD，这与人类通常使用的高蛋白 KD 不同。肝脏在酮适应中起着重要作用，因为它参与糖异生和酮生成。本研究旨在检验以下假设：在摄入正常蛋白 KD（NPKD）的同时进行运动训练（ExTr），将在肝脏代谢途径中引起附加/协同反应。
给予 lean、健康的雄性 C57BL/6J 小鼠低脂对照饮食（15.9% 蛋白卡路里，11.9% 脂肪卡路里，72.2% 碳水化合物卡路里）或碳水化合物缺乏的 NPKD（16.1% 蛋白，83.9% 脂肪卡路里）6 周。在饮食 3 周后，一半的小鼠进行 3 周的跑步机 ExTr（5 天/周，60 分钟/天，中等强度到剧烈强度）。实验结束时，在肝脏和胰腺中测试与底物代谢相关的代谢和内分泌结果。
NPKD 喂养的小鼠具有更高的循环 β-羟丁酸水平，并在休息和运动期间维持血糖水平。NPKD 喂养的小鼠具有更低的丙酮酸利用率和更大的生酮潜力，表现为更高的氧化率来分解脂质（线粒体和过氧化物酶体）和生酮氨基酸（亮氨酸）。ExTr 增加了糖异生基因 Pck1 的表达，但肝脏糖原、丙酮酸氧化、不完全脂肪氧化和胰腺总面积降低。NPKD 和 ExTr 之间存在肝内甘油三酯以及参与糖异生、酮生成、线粒体脂肪氧化和过氧化物酶体标志物的基因的相互作用效应；然而，没有一个是附加/协同的。相反，在每种情况下，相互作用效应都表明 NPKD 和 ExTr 相互拮抗。
NPKD 和 ExTr 独立地诱导肝脏代谢途径的转变，但在健康小鼠中，这些变化似乎不是附加/协同的。
