Laboratory of Molecular Metabolism, The Rockefeller University, New York (M.K., P.C.).
Dalton Cardiovascular Research Center, University of Missouri, Columbia (M.A.H., J.R.S.).
Circ Res. 2021 Apr 2;128(7):951-968. doi: 10.1161/CIRCRESAHA.121.318093. Epub 2021 Apr 1.
Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.
心血管疾病是全球范围内的主要死亡原因。超重和肥胖与高血压和胰岛素抵抗等合并症密切相关,这些合并症共同导致了心血管疾病的发生,以及由此产生的发病率和死亡率。美国有 42%的成年人肥胖,而全球共有 19 亿成年人超重或肥胖。这些令人震惊的数字还在不断攀升,这代表着一个重大的健康和经济负担。脂肪组织是一个高度动态的器官,可以根据不同部位的细胞组成及其独特的解剖定位进行分类。肥胖时脂肪组织的大量扩张和重塑会对特定的脂肪组织部位产生不同的影响,并显著导致血管功能障碍和心血管疾病。内脏脂肪组织的积累会导致免疫细胞浸润和血管收缩介质的分泌增加,而皮下脂肪组织的扩张则危害较小。因此,脂肪分布(而不是总体体重)是心血管疾病风险的关键决定因素。与白色脂肪组织相比,产热的棕色和米色脂肪组织与对血管的有益影响有关。在血管周围脂肪组织异质表型的背景下,脂肪组织的类型与其对血管功能的影响之间的关系变得尤为明显,这种表型强烈依赖于位置。在这篇综述中,我们讨论了肥胖过程中特定脂肪组织部位的异常重塑,以及这如何对高血压、内皮功能障碍和血管僵硬的发展产生重大影响。我们还讨论了肥胖期间脂肪组织来源的分泌因子和全身性炎症增加的局部和全身作用,并强调了它们对心血管健康的有害影响。