Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.
Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.
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DOI：
10.1161/circulationaha.110.970145
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发表时间：
2011-01-18
期刊：
影响因子：
37.8
通讯作者：
Corvera S
中科院分区：
文献类型：
--
作者：
Gealekman O;Guseva N;Hartigan C;Apotheker S;Gorgoglione M;Gurav K;Tran KV;Straubhaar J;Nicoloro S;Czech MP;Thompson M;Perugini RA;Corvera S
脂肪组织因热量摄入过多而膨胀，但倾向于存款内脏（维斯）而不是皮下（SQ）脂肪组织的个体患代谢疾病的风险更高。血管生成在人类脂肪组织库的可扩展性中的作用尚不清楚。本研究的目的是测量维斯和SQ脂肪组织中的血管生成，并确定肥胖、代谢状态和这些贮库的血管生成特性之间是否存在关系。通过定量包埋在Matrigel中的人脂肪组织外植体的毛细血管分支形成来确定血管生成能力，并通过免疫组织化学评估毛细血管密度。与维斯相比，SQ脂肪组织具有更大的血管生成能力，即使在正常化至其更高的初始毛细血管密度后。基因阵列分析揭示了贮库之间血管生成基因表达的显著差异，包括ANGPTL4的SQ表达增加，ANGPTL4在脂肪组织背景下是促血管生成的。SQ毛细血管密度和血管生成能力随着病态肥胖而降低，SQ，而不是维斯，脂肪组织血管生成能力与胰岛素敏感性呈负相关。这些数据意味着SQ脂肪组织与维斯相比具有更高的扩张其毛细血管网络的能力，但这种能力随着病态肥胖而降低。这种减少与胰岛素抵抗相关，表明SQ脂肪组织血管生成的损害可能有助于代谢性疾病的发病机制。
Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral (VIS) instead of subcutaneous (SQ) adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in VIS and SQ adipose tissue, and to establish whether there is a relationship between obesity, metabolic status and the angiogenic properties of these depots. Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. SQ adipose tissue had a greater angiogenic capacity compared to VIS, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased SQ expression of ANGPTL4, which is pro-angiogenic in an adipose tissue context. SQ capillary density and angiogenic capacity decreased with morbid obesity, and SQ, but not VIS, adipose tissue angiogenic capacity negatively correlated with insulin sensitivity. These data imply that SQ adipose tissue has a higher capacity to expand its capillary network compared to VIS, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of SQ adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.