Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
Mol Metab. 2019 Jul;25:11-19. doi: 10.1016/j.molmet.2019.04.002. Epub 2019 Apr 10.
Thermogenic adipocytes reorganize their metabolism during cold exposure. Metabolic reprogramming requires readily available bioenergetics substrates, such as glucose and fatty acids, to increase mitochondrial respiration and produce heat via the uncoupling protein 1 (UCP1). This condition generates a finely-tuned production of mitochondrial reactive oxygen species (ROS) that support non-shivering thermogenesis.
Herein, the findings underlining the mechanisms that regulate ROS production and control of the adaptive responses tuning thermogenesis in adipocytes are described. Furthermore, this review describes the metabolic responses to substrate availability and the consequence of mitochondrial failure to switch fuel oxidation in response to changes in nutrient availability. A framework to control mitochondrial ROS threshold to maximize non-shivering thermogenesis in adipocytes is provided.
Thermogenesis synchronizes fuel oxidation with an acute and transient increase of mitochondrial ROS that promotes the activation of redox-sensitive thermogenic signaling cascade and UCP1. However, an overload of substrate flux to mitochondria causes a massive and damaging mitochondrial ROS production that affects mitochondrial flexibility. Finding novel thermogenic redox targets and manipulating ROS concentration in adipocytes appears to be a promising avenue of research for improving thermogenesis and counteracting metabolic diseases.
产热脂肪细胞在寒冷暴露时会重新调整其代谢。代谢重编程需要可利用的生物能量底物，如葡萄糖和脂肪酸，以增加线粒体呼吸并通过解偶联蛋白 1（UCP1）产热。这种情况会产生精细调节的线粒体活性氧（ROS）产生，从而支持不颤抖的产热。
本文描述了调节 ROS 产生的机制以及控制脂肪细胞中产热适应性反应的调节，这些发现阐明了这一点。此外，本综述描述了对底物可用性的代谢反应，以及线粒体未能根据营养物质可用性的变化切换燃料氧化的后果。提供了一个控制线粒体 ROS 阈值的框架，以最大限度地提高脂肪细胞中的非颤抖产热。
产热将燃料氧化与线粒体 ROS 的急性和短暂增加同步，促进了氧化还原敏感的产热信号级联和 UCP1 的激活。然而，底物通量对线粒体的过载会导致大量和破坏性的线粒体 ROS 产生，从而影响线粒体的灵活性。寻找新的产热氧化还原靶标并在脂肪细胞中操纵 ROS 浓度似乎是改善产热和对抗代谢疾病的有前途的研究途径。
