当前位置: X-MOL 学术Cardiovasc. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans
Cardiovascular Research ( IF 10.8 ) Pub Date : 2022-08-09 , DOI: 10.1093/cvr/cvac131
Zhixiong Ying 1 , Naomi Tramper 1 , Enchen Zhou 1 , Mariëtte R Boon 1 , Patrick C N Rensen 1 , Sander Kooijman 1
Affiliation  

Brown adipocytes within brown adipose tissue (BAT) and beige adipocytes within white adipose tissue dissipate nutritional energy as heat. Studies in mice have shown that activation of thermogenesis in brown and beige adipocytes enhances the lipolytic processing of triglyceride-rich lipoproteins (TRLs) in plasma to supply these adipocytes with fatty acids for oxidation. This process results in formation of TRL remnants that are removed from the circulation through binding of apolipoprotein E (ApoE) on their surface to the low-density lipoprotein receptor (LDLR) on hepatocytes, followed by internalization. Concomitantly, lipolytic processing of circulating TRLs leads to generation of excess surface phospholipids that are transferred to nascent high-density lipoproteins (HDL), increasing their capacity for reverse cholesterol transport. Activation of thermogenic adipocytes thus lowers circulating triglycerides and non-HDL-cholesterol, while it increases HDL-cholesterol. The combined effect is protection from atherosclerosis development, which becomes evident in humanized mouse models with an intact ApoE-LDLR clearance pathway only, and is additive to the effects of classical lipid-lowering drugs including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. A large recent study revealed that the presence of metabolically active BAT in humans is associated with lower triglycerides, higher HDL-cholesterol and lower risk of cardiovascular diseases. This narrative review aims to provide leads for further exploration of thermogenic adipose tissue as a therapeutic target. To this end, we describe the latest knowledge on the role of BAT in lipoprotein metabolism and address, for example, the discovery of the β2-adrenergic receptor as the dominant adrenergic receptor in human thermogenic adipocytes.

中文翻译:

产热脂肪组织在脂质代谢和动脉粥样硬化性心血管疾病中的作用:来自小鼠和人类研究的经验教训

棕色脂肪组织 (BAT) 内的棕色脂肪细胞和白色脂肪组织内的米色脂肪细胞以热量的形式消耗营养能量。对小鼠的研究表明,激活棕色和米色脂肪细胞中的生热作用可增强血浆中富含甘油三酯的脂蛋白 (TRL) 的脂解过程,从而为这些脂肪细胞提供用于氧化的脂肪酸。该过程导致形成 TRL 残留物,通过将其表面的载脂蛋白 E (ApoE) 结合到肝细胞上的低密度脂蛋白受体 (LDLR),然后内化,这些残留物从循环中去除。同时,循环 TRL 的脂解处理导致产生过量的表面磷脂,这些磷脂被转移到新生的高密度脂蛋白 (HDL),从而增加它们逆向转运胆固醇的能力。因此,产热脂肪细胞的激活降低了循环甘油三酯和非高密度脂蛋白胆固醇,同时增加了高密度脂蛋白胆固醇。综合作用是防止动脉粥样硬化的发展,这在仅具有完整 ApoE-LDLR 清除途径的人源化小鼠模型中变得明显,并且是经典降脂药物(包括他汀类药物和前蛋白转化酶枯草杆菌蛋白酶/kexin 9 抑制剂)作用的补充。最近的一项大型研究表明,人体中具有代谢活性的 BAT 与较低的甘油三酯、较高的高密度脂蛋白胆固醇和较低的心血管疾病风险有关。这篇叙述性综述旨在为进一步探索产热脂肪组织作为治疗靶点提供线索。为此,
更新日期:2022-08-09
down
wechat
bug