Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects
Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects
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DOI：
10.1210/jc.2015-4125
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发表时间：
2016-04-01
影响因子：
5.8
通讯作者：
Rasouli, Neda
中科院分区：
文献类型：
--
作者：
Lawler, Helen M.;Underkofler, Chantal M.;Rasouli, Neda
背景：相当数量的肥胖个体相对胰岛素敏感，这种变异的病因尚不清楚。目的：检测脂肪组织中区分肥胖胰岛素敏感（OBIS）和肥胖胰岛素抵抗（OBIR）个体的因素，探讨脂肪组织缺氧是否在胰岛素抵抗的发病机制中起作用。设计与环境：这是一项普通社区的横断面研究。参与者：受试者由体重指数、年龄、体脂相近但胰岛素敏感性指数不同的非糖尿病OBIS和OBIR受试者以及瘦胰岛素敏感性受试者组成。干预措施：无干预措施。主要观察指标：我们检测了脂肪细胞因子和候选基因在脂肪组织和脂肪组织氧合中调节缺氧、炎症和脂肪生成的表达。结果：与OBIR受试者相比，OBIS受试者血浆脂联素升高，但血浆TNF α和瘦素水平相似。在OBIR组和OBIS组中，调节炎症的基因（CD68、MCP1、清除率受体A和氧化LDL受体1）增加了40%-60% （P < 0.05）。此外，参与细胞外基质形成的基因，如胶原VI和MMP7，在OBIR和OBIS中分别上调43%和78% （P < 0.05）。与OBIS相比，OBIR组HIF1 α和VEGF基因表达分别升高37%和52% （P < 0.01）。尽管低氧相关基因的表达存在差异，但通过Licox氧探针测量的脂肪组织氧合在OBIS和OBIR受试者之间没有差异，但瘦受试者的脂肪组织氧合高于肥胖受试者。结论：我们证实脂肪组织炎症和纤维化在人类独立于肥胖的胰岛素抵抗发病机制中起重要作用。缺氧是否仅仅是脂肪组织扩张的结果，还是与肥胖引起的胰岛素抵抗的发病机制有关，目前尚不清楚。
Context: A substantial number of obese individuals are relatively insulin sensitive and the etiology for this variation remains unknown.Objective: The primary objective was to detect factors in adipose tissue differentiating obese insulin-sensitive (OBIS) from obese insulin-resistant (OBIR) individuals and investigate whether adipose tissue hypoxia is a contributing factor in the pathogenesis of insulin resistance.Design and Setting: This was a cross-sectional study in the general community.Participants: Subjects consisted of nondiabetic OBIS and OBIR subjects with similar body mass index, age, and total body fat but different insulin sensitivity index as well as lean insulin-sensitive subjects.Intervention(s): There were no interventions.Main Outcome Measure(s): We examined adipocytokines and the expression of candidate genes regulating hypoxia, inflammation, and lipogenesis in adipose tissue and adipose tissue oxygenation.Results: OBIS subjects had increased plasma adiponectin but similar plasma TNF alpha and leptin levels as compared with OBIR subjects. Genes regulating inflammation (CD68, MCP1, scavenger receptor A, and oxidized LDL receptor 1) were increased by 40%-60% (P < .05) in OBIR vs OBIS cohorts. In addition, genes involved in extracellular matrix formation such as collagen VI and MMP7 were up-regulated by 43% and 78% (P < .05), respectively, in OBIR vs OBIS. The expression of HIF1 alpha and VEGF gene expression was increased by 37% and 52%, respectively, in OBIR vs OBIS (P < .01). Despite the differential expression in hypoxia-related genes, adipose tissue oxygenation measured by a Licox oxygen probe was not different between OBIS and OBIR subjects, but it was higher in lean subjects as compared with obese subjects.Conclusions: We confirmed that adipose tissue inflammation and fibrosis play an important role in the pathogenesis of insulin resistance independent of obesity in humans. Whether hypoxia is simply a consequence of adipose tissue expansion or is related to the pathogenesis of obesity-induced insulin resistance is yet to be understood.