Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of “inter-organ mitohormesis.” Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity.

脂肪细胞在肥胖中承受强烈的能量压力，导致线粒体质量和功能丧失。我们发现脂肪细胞通过快速而有力地释放小的细胞外囊泡 (sEV) 来响应线粒体压力。这些 sEV 含有具有呼吸能力但被氧化损伤的线粒体颗粒，这些颗粒进入循环并被心肌细胞吸收，在那里它们会引发 ROS 的爆发。结果是心脏中的补偿性抗氧化信号传导保护心肌细胞免受急性氧化应激，与预处理范例一致。因此，单次注射来自能量压力脂肪细胞的 sEV 可限制小鼠的心脏缺血/再灌注损伤。这项研究首次描述了组织之间的功能性线粒体转移，以及“器官间有丝分裂”的第一个脊椎动物例子。因此，这些看似有毒的脂肪细胞 sEV 可能提​​供有效的心脏保护的生理途径，以防止肥胖引起的不可避免的脂毒性或缺血性应激。