Adipose organ is made of white (WAT) and brown (BAT) adipose tissue which are primarily responsible for lipid storage and energy production (heat and ATP) respectively. Metabolic activation of WAT may ascribe to this tissue characteristics of BAT, namely non-shivering thermogenesis and ATP production. Recent data indicate that apolipoproteins E (APOE) and A1 (APOA1) regulate WAT mitochondrial metabolic activation. Here, we investigated the functional cross-talk between natural human APOE2 and APOE4 isoforms with APOA1 in this process, using Apoe2knock-in and Apoe4knock-in mice. At baseline when Apoe2knock-in and Apoe4knock-in mice express both APOE and Apoa1, the Apoe2knock-in strain appears to have higher mitochondrial oxidative phosphorylation levels and non-shivering thermogenesis in WAT compared to Apoe4knock-in mice. When mice were switched to a high-fat diet for 18 weeks, circulating levels of endogenous Apoa1 in Apoe2knock-in mice became barely detectable though significant levels of APOE2 were still present. This change was accompanied by a significant reduction in WAT mitochondrial Ucp1 expression while BAT Ucp1 was unaffected. Ectopic APOA1 expression in Apoe2knock-in animals potently stimulated WAT but not BAT mitochondrial Ucp1 expression providing further evidence that APOA1 potently stimulates WAT non-shivering thermogenesis in the presence of APOE2. Ectopic expression of APOA1 in Apoe4knock-in mice stimulated BAT but no WAT mitochondrial Ucp1 levels, suggesting that in the presence of APOE4, APOA1 is a trigger of BAT non-shivering thermogenesis. Overall, our data identified a tissue-specific role of the natural human APOE2 and APOE4 isoforms in WAT- and BAT-metabolic activation respectively, that appears dependent on circulating APOA1 levels.

中文翻译：

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载脂蛋白E对脂肪组织代谢活化的同工型和组织依赖性影响：载脂蛋白A1的作用。

脂肪器官由白色（WAT）和棕色（BAT）脂肪组织组成，它们分别负责脂质的储存和能量的产生（热量和ATP）。WAT的代谢活化可能归因于BAT的组织特征，即非颤抖的生热作用和ATP产生。最近的数据表明载脂蛋白E（APOE）和A1（APOA1）调节WAT线粒体的代谢活化。在这里，我们使用Apoe2knock-in和Apoe4knock-in小鼠研究了自然人APOE2和APOE4亚型与APOA1之间的功能性串扰。在基线时，当Apoe2基因敲入小鼠和Apoe4基因敲入小鼠同时表达APOE和Apoa1时，与Apoe4基因敲入小鼠相比，Apoe2基因敲入菌株在WAT中似乎具有更高的线粒体氧化磷酸化水平和无颤抖的生热作用。当小鼠改用高脂饮食持续18周时，虽然仍然存在大量的APOE2，但几乎无法检测到Apoe2基因敲入小鼠中内源性Apoa1的循环水平。这种变化伴随着WAT线粒体Ucp1表达的显着降低，而BAT Ucp1不受影响。Apoe2基因敲入动物中的异位APOA1表达有效刺激了WAT，但BAT线粒体Ucp1表达却没有刺激，这提供了进一步的证据表明APOA1在APOE2存在的情况下可以有效刺激WAT非发抖的生热作用。Apoe4基因敲入小鼠中APOA1的异位表达刺激BAT，但没有WAT线粒体Ucp1水平，这表明存在APOE4时，APOA1是BAT非颤动生热的触发因素。全面的，