Emerging Roles for Adipose Tissue in Cardiovascular Disease.
Emerging Roles for Adipose Tissue in Cardiovascular Disease.
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DOI：
10.1161/atvbaha.118.311421
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Bauer RC
中科院分区：
文献类型：
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作者：
Ha EE;Bauer RC
e138 Arterioscler Thromb Vasc Biol 2018年8月这两项研究之间的主要差异是Gao等人10关注正常钠水平差异的长期影响，而第二份报告关注更极端的高钠水平模型。近年来的研究发现，脂肪细胞通过ABCA 1（ATP结合盒转运蛋白A1）转运蛋白将胆固醇外排，从而直接影响HDL-C水平。14 Cuffe等人15产生了脂肪细胞特异性Abca 1敲除小鼠，并观察到这些小鼠的血浆总胆固醇和HDL-C水平降低;此外，这些小鼠的脂肪胆固醇含量增加了3倍，特别是在脂肪细胞的质膜中，突出了Abca 1在脂肪细胞胆固醇通量中的重要性。有趣的是，小鼠表现出减弱的饮食诱导的肥胖，以及减少脂肪细胞肥大，TG积累和从头脂肪生成。考虑到HDL-C水平和肥胖之间的一般负相关性，以及先前的观察结果，即脂肪细胞胆固醇增加与脂肪细胞肥大和TG积累增加有关，这是令人惊讶的。17正如Cuffe等人所指出的和la Rose等人所编辑的，18这项研究指出了膜胆固醇通过SREBP（固醇调节元件结合蛋白）途径在脂肪细胞脂质调节中的重要作用。此外，ABCA 1转运蛋白的作用可能是细胞依赖性的，ABCA 1缺乏导致的疾病状态（即丹吉尔病）是缺乏巨噬细胞和脂肪细胞胆固醇流出的综合效应。考虑到脂肪组织的细胞异质性，使用细胞特异性模型，如本研究中使用的模型，对于理解脂肪组织调节脂质的机制至关重要。
e138 Arterioscler Thromb Vasc Biol August 2018 major difference between these 2 studies is Gao et al’s10 focus on long-term effects of variances in normal levels of sodium levels, whereas the second report focused on a more extreme model of high sodium levels. Further studies would be needed to understand the mechanism of hypertonicity on adipocyte lipid accumulation.Recent studies have identified that adipocytes can directly affect HDL-C levels via efflux of cholesterol through the ABCA1 (ATP-binding cassette transporter A1) transporter. 14 Cuffe et al15 generated adipocyte-specific Abca1 knockout mice and observed that these mice have decreased plasma total cholesterol and HDL-C levels; additionally, these mice had 3-fold increased adipose cholesterol content, especially in the plasma membranes of adipocytes, highlighting the importance of Abca1 in adipocyte cholesterol flux. Interestingly, the mice exhibited attenuated dietinduced obesity, as well as decreased adipocyte hypertrophy, TG accumulation, and de novo lipogenesis. This is surprising, given the general negative association between HDL-C levels and obesity, 16 as well as previous observations that increased adipocyte cholesterol associates with adipocyte hypertrophy and increased TG accumulation. 17 As pointed out by Cuffe et al and editorialized by la Rose et al, 18 this study points out an important role specifically for membrane cholesterol in adipocyte lipid regulation through the SREBP (sterol regulatory element-binding protein) pathways. Additionally, the role of the ABCA1 transporter is likely cell dependent, and disease states (ie, Tangier disease) resulting from ABCA1 deficiency are a combination of effects from lack of cholesterol efflux from both macrophages and adipocytes. Given the cellular heterogeneity of adipose tissue, the use of cell-specific models, such as those used in this study, is critical for understanding mechanisms of adipose tissue regulation of lipids.