School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
FASEB J. 2020 Mar;34(3):4602-4618. doi: 10.1096/fj.201902594RR. Epub 2020 Feb 6.
Understanding the mechanisms regulating mitochondrial respiratory function and adaptations to metabolic challenges, such as exercise and high dietary fat, is necessary to promote skeletal muscle health and attenuate metabolic disease. Autophagy is a constitutively active degradation pathway that promotes mitochondrial turnover and transiently increases postexercise. Recent evidence indicates Bcl2 mediates exercise-induced autophagy and skeletal muscle adaptions to training during high-fat diet. We determined if improvements in mitochondrial respiration due to exercise training required Bcl2-mediated autophagy using a transgenic mouse model of impaired inducible autophagy (Bcl2 ). Mitochondrial adaptations to a treadmill exercise training protocol, in either low-fat or high-fat diet fed mice, did not require Bcl2-mediated autophagy activation. Instead, training increased protein synthesis rates and basal autophagy in the Bcl2 mice, while acute exercise activated BNIP3 and Parkin autophagy. High-fat diet stimulated lipid-specific mitochondrial adaptations. These data demonstrate increases in basal mitochondrial turnover, not transient activation with exercise, mediate adaptations to exercise and high-fat diet.
了解调节线粒体呼吸功能和适应代谢挑战（如运动和高脂肪饮食）的机制对于促进骨骼肌健康和减轻代谢疾病至关重要。自噬是一种持续活跃的降解途径，可促进线粒体周转，并在运动后短暂增加。最近的证据表明，Bcl2 介导运动诱导的自噬和高脂肪饮食期间的训练对骨骼肌的适应。我们使用诱导自噬缺陷的转基因小鼠模型（Bcl2 ）确定由于运动训练而导致的线粒体呼吸改善是否需要 Bcl2 介导的自噬。在低脂或高脂饮食喂养的小鼠中，跑步机运动训练方案对线粒体的适应并不需要 Bcl2 介导的自噬激活。相反，训练增加了 Bcl2 小鼠的蛋白质合成率和基础自噬，而急性运动激活了 BNIP3 和 Parkin 自噬。高脂肪饮食刺激了脂质特异性的线粒体适应。这些数据表明，基础线粒体周转率的增加，而不是运动时的短暂激活，介导了对运动和高脂肪饮食的适应。
