Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. Notably, we found that the ketolytic enzyme beta-hydroxybutyrate dehydrogenase 1 (BDH1) is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (FAO). Using mice with BDH1 deficiency in striated muscles, we discover that this enzyme optimizes FAO efficiency and exercise tolerance during acute fasting. Additionally, iTRF leads to robust molecular remodeling of muscle tissues, and muscle BDH1 flux does indeed play an essential role in conferring the full adaptive benefits of this regimen, including increased lean mass, mitochondrial hormesis, and metabolic rerouting of pyruvate. In sum, ketone flux enhances mitochondrial bioenergetics and supports iTRF-induced remodeling of skeletal muscle and heart.

中文翻译：

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通过 BDH1 的酮流支持骨骼和心肌的代谢重塑，以响应间歇性限时进食


限时喂养（TRF）作为一种促进代谢健康的饮食疗法已引起人们的关注。这项研究质疑间歇性 TRF (iTRF) 计划的健康益处是否需要骨骼和心肌中的酮通量。值得注意的是，我们发现酮解酶 β-羟基丁酸脱氢酶 1 (BDH1) 在源自心脏和红色/氧化骨骼肌的分离线粒体中独特富集，这些线粒体也具有较高的脂肪酸氧化 (FAO) 能力。通过使用横纹肌中 BDH1 缺乏的小鼠，我们发现这种酶可以优化急性禁食期间的FAO效率和运动耐量。此外，iTRF 会导致肌肉组织的强有力的分子重塑，并且肌肉 BDH1 通量确实在赋予该方案的完全适应性益处方面发挥着重要作用，包括增加瘦体重、线粒体兴奋效应和丙酮酸的代谢重新路由。总之，酮通量增强线粒体生物能并支持 iTRF 诱导的骨骼肌和心脏重塑。