University of Patras School of Health Sciences, Department of Medicine, Pharmacology Laboratory, Panepistimioupolis, Rio, Greece.
University of Patras School of Health Sciences, Department of Medicine, Pharmacology Laboratory, Panepistimioupolis, Rio, Greece; European University Cyprus, School of Sciences, Department of Life Sciences, Nicosia, Cyprus.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Mar;1866(3):158859. doi: 10.1016/j.bbalip.2020.158859. Epub 2020 Dec 11.
White (WAT) and brown (BAT) adipose tissue, the two main types of adipose organ, are responsible for lipid storage and non-shivering thermogenesis, respectively. Thermogenesis is a process mediated by mitochondrial uncoupling protein 1 (UCP1) which uncouples oxidative phosphorylation from ATP production, leading to the conversion of free fatty acids to heat. This process can be triggered by exposure to low ambient temperatures, caloric excess, and the immune system. Recently mitochondrial thermogenesis has also been associated with plasma lipoprotein transport system. Specifically, apolipoprotein (APO) E3 is shown to have a bimodal effect on WAT thermogenesis that is highly dependent on its site of expression. Similarly, APOE2 and APOE4 differentially affect BAT and WAT mitochondrial metabolic activity in processes highly modulated by APOA1. Furthermore, the absence of classical APOA1 containing HDL (APOA1-HDL), is associated with no measurable non-shivering thermogenesis in WAT of mice fed high fat diet. Based on these previous observations which indicate important regulatory roles for both APOA1 and APOE in adipose tissue mitochondrial metabolic activity, here we sought to investigate the potential roles of these apolipoproteins in BAT and WAT metabolic activation in mice, following stimulation by cold exposure (7 °C). Our data indicate that APOA1-HDL promotes metabolic activation of BAT only in the presence of very low levels (virtually undetectable) of APOE3-containing HDL (APOE3-HDL), which acts as an inhibitor in this process. In contrast, induction of WAT thermogenesis is subjected to a more complicated regulation which requires the combined presence of both APOA1-HDL and APOE3-HDL.
白色（WAT）和棕色（BAT）脂肪组织是两种主要的脂肪器官，分别负责脂质储存和非颤抖性产热。产热是由线粒体解偶联蛋白 1（UCP1）介导的过程，它将氧化磷酸化与 ATP 产生解偶联，导致游离脂肪酸转化为热量。这个过程可以通过暴露在低温、热量过剩和免疫系统中触发。最近，线粒体产热也与血浆脂蛋白转运系统有关。具体来说，载脂蛋白（APO）E3 对 WAT 产热有双峰效应，高度依赖于其表达部位。同样，APOE2 和 APOE4 对 BAT 和 WAT 线粒体代谢活性的影响不同，这一过程高度受 APOA1 的调节。此外，缺乏经典的载脂蛋白 A1 含高密度脂蛋白（APOA1-HDL），与高脂肪饮食喂养的小鼠 WAT 中不可测量的非颤抖性产热无关。基于这些先前的观察结果表明，APOA1 和 APOE 在脂肪组织线粒体代谢活性中具有重要的调节作用，在这里，我们试图研究这些载脂蛋白在冷暴露（7°C）刺激下对 BAT 和 WAT 代谢激活的潜在作用。我们的数据表明，APOA1-HDL 仅在极低水平（几乎无法检测到）的载脂蛋白 E3 含高密度脂蛋白（APOE3-HDL）存在的情况下促进 BAT 的代谢激活，而 APOE3-HDL 在这个过程中起抑制作用。相比之下，WAT 产热的诱导受到更复杂的调节，需要 APOA1-HDL 和 APOE3-HDL 的共同存在。
