Changes in mitochondrial function in a variety of cells/tissues are critical for orchestrating systemic energy homeostasis and are linked to the development of obesity and many of its comorbidities. The mitochondrial translocator protein of 18 kDa (TSPO) is expressed in organs throughout the body, including the brain, liver, adipose tissue, gonads and adrenal glands, where it is implicated in regulating steroidogenesis and cellular metabolism. Prior work from our group and others has shown that, in rodents, TSPO levels are altered in adipose tissue by obesity and that modulation of TSPO activity may impact systemic glucose homeostasis. Furthermore, in vitro studies in a variety of cell types have implicated TSPO in mediating cellular energetics and substrate utilisation. Although mice with germline global TSPO deficiency (TSPO^−/−) have no reported changes in body weight under standard husbandry conditions, we hypothesised that, given the roles of TSPO in regulating mitochondrial function and cellular metabolic flexibility, these animals may have alterations in their systemic response to altered energy availability, either nutritional excess or insufficiency. In agreement with published work, compared to wild-type (TSPO^+/+) littermates, TSPO^−/− mice of both sexes did not exhibit differences in body weight on standard chow. Furthermore, following a 12-hour overnight fast, there was no difference in weight loss or compensatory food intake during re-feeding. Five weeks of feeding a high-fat diet (HFD) did not reveal any impact of the absence of TSPO on body weight gain in either male or female mice. Basal blood glucose levels and glucose clearance in a glucose tolerance test were influenced by feeding a HFD diet but not by genotype. In conclusion, in the paradigms examined, germline global deletion of TSPO did not change the physiological response to deviations in systemic energy availability at the whole organism level.

中文翻译：

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小鼠中线粒体转运蛋白 18 kDa 的缺失不影响体重或食物摄入对能量可用性改变的反应

各种细胞/组织中线粒体功能的变化对于协调全身能量稳态至关重要，并且与肥胖及其许多合并症的发展有关。18 kDa 的线粒体转运蛋白 (TSPO) 在全身器官中表达，包括大脑、肝脏、脂肪组织、性腺和肾上腺，在这些器官中它参与调节类固醇生成和细胞代谢。我们小组和其他人的先前工作表明，在啮齿动物中，脂肪组织中的 TSPO 水平会因肥胖而改变，并且 TSPO 活性的调节可能会影响全身葡萄糖稳态。此外，对多种细胞类型的体外研究表明 TSPO 参与介导细胞能量学和底物利用。尽管种系全局 TSPO 缺乏症（TSPO^-/- ) 在标准饲养条件下没有报告体重变化，我们假设，鉴于 TSPO 在调节线粒体功能和细胞代谢灵活性方面的作用，这些动物可能会改变它们对改变的能量可用性的全身反应，无论是营养过剩或不足。与已发表的工作一致，与野生型 (TSPO ^+/+ ) 同窝仔猪相比，TSPO ^-/-两种性别的小鼠在标准食物上都没有表现出体重差异。此外，经过 12 小时的隔夜禁食，在重新喂食期间体重减轻或补偿性食物摄入量没有差异。喂食高脂肪饮食 (HFD) 五周后，无论雄性还是雌性小鼠，都没有发现 TSPO 缺乏对体重增加的任何影响。葡萄糖耐量试验中的基础血糖水平和葡萄糖清除率受喂食 HFD 饮食的影响，但不受基因型的影响。总之，在研究的范式中，TSPO 的种系全局缺失并未改变对整个生物体水平上系统能量可用性偏差的生理反应。