Exogenous mitochondrial transfer increases energy expenditure and attenuates adiposity gains in mice with diet-induced obesity.
Exogenous mitochondrial transfer increases energy expenditure and attenuates adiposity gains in mice with diet-induced obesity.
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外源性线粒体转移会增加饮食引起的肥胖小鼠的能量消耗并减弱肥胖的增加。
DOI：
10.1101/2023.12.23.573206
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bajwa,Amandeep
中科院分区：
文献类型：
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作者：
Namwanje,Maria;Mazumdar,Soumi;Stayton,Amanda;Patel,PrishaS;Watkins,Christine;White,Catrina;Brown,Chester;Eason,JamesD;Mozhui,Khyobeni;Kuscu,Cem;Pabla,Navjot;Stephenson,ErinJ;Bajwa,Amandeep
肥胖与慢性多系统生物能量应激有关，通过增加器官系统中健康线粒体的数量可以改善这种情况。然而，能够增加线粒体含量的治疗方法通常仅限于耐力运动训练模式，这种模式并不总是长期可持续的，更不用说对许多肥胖症患者来说是可行的。最近的研究表明，从健康的供体组织中局部移植外源线粒体可以改善器官特异性疾病受体的生物能量结果，减轻组织损伤的影响。因此，本项目的目的是确定在饮食诱导肥胖的背景下，系统线粒体转移改善能量平衡调节的可行性。我们发现，将瘦小鼠的线粒体移植到饮食诱导肥胖的小鼠体内，通过增加能量消耗和促进脂质的动员和氧化来减缓肥胖的增加。此外，接受外源性线粒体的小鼠表现出更好的葡萄糖摄取，更强的胰岛素反应性，以及肝脏脂肪变性的完全逆转。这些变化在一定程度上是由白色脂肪组织中发生的适应所驱动的。总之，这些发现证明了线粒体移植是一种有效的治疗策略，可以限制饮食诱导的肥胖对小鼠的有害代谢影响。
Obesity is associated with chronic multi-system bioenergetic stress that may be improved by increasing the number of healthy mitochondria available across organ systems. However, treatments capable of increasing mitochondrial content are generally limited to endurance exercise training paradigms, which are not always sustainable long-term, let alone feasible for many patients with obesity. Recent studies have shown that local transfer of exogenous mitochondria from healthy donor tissues can improve bioenergetic outcomes and alleviate the effects of tissue injury in recipients with organ specific disease. Thus, the aim of this project was to determine the feasibility of systemic mitochondrial transfer for improving energy balance regulation in the setting of diet-induced obesity. We found that transplantation of mitochondria from lean mice into mice with diet-induced obesity attenuated adiposity gains by increasing energy expenditure and promoting the mobilization and oxidation of lipids. Additionally, mice that received exogenous mitochondria demonstrated improved glucose uptake, greater insulin responsiveness, and complete reversal of hepatic steatosis. These changes were, in part, driven by adaptations occurring in white adipose tissue. Together, these findings are proof-of-principle that mitochondrial transplantation is an effective therapeutic strategy for limiting the deleterious metabolic effects of diet-induced obesity in mice.