Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation
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DOI：
10.1073/pnas.1121060109
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发表时间：
2012-04-24
影响因子：
11.1
通讯作者：
Jain, Mukesh K.
中科院分区：
文献类型：
--
作者：
Haldar, Saptarsi M.;Jeyaraj, Darwin;Jain, Mukesh K.
骨骼肌在运动过程中提高脂质利用的能力是生存所必需的代谢可塑性的一种形式。相反，肌肉中的代谢紊乱会导致器官功能障碍和疾病。虽然转录因子Kruppel样因子15（KLF15）是葡萄糖和氨基酸代谢的重要调节因子，但其在脂质稳态和肌肉生理学中的内源性作用尚不清楚。在这里，我们证明KLF15是必不可少的骨骼肌脂质利用和生理性能。KLF15直接调节广泛的转录程序，跨越肌肉中脂质通量途径的所有主要部分。因此，Klf15缺陷小鼠具有异常的脂质和能量通量、过度依赖碳水化合物燃料、过度的肌肉疲劳和受损的耐力运动能力。对KLF15这一迄今未被认识的作用的阐明现在暗示该因子是转录回路的中心组成部分，其协调所有三种基本细胞营养物（葡萄糖、氨基酸和脂质）的生理通量。
The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids.