肥胖个体内脏和皮下脂肪组织中共同表达的免疫和代谢基因与血浆高密度脂蛋白和血糖水平相关：一项基因芯片研究。

BACKGROUND: Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots. METHODS: Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol. RESULTS: Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 x 10(-5)). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 x 10(-5)). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified. CONCLUSIONS: In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.

背景：体脂肪过度积累，特别是内脏脂肪库，是导致多种疾病（如 2 型糖尿病）的主要风险因素。肥胖个体患合并症的风险增加的机制在很大程度上尚不清楚。我们旨在确定在皮下脂肪组织（SAT）和内脏脂肪组织（VAT）中表达的基因，这些基因与肥胖合并症相关的血液参数有关，如血浆脂质和血糖水平，并比较脂肪组织之间的基因表达。

方法：在 75 名 BMI>35kg/m2 的个体中，测定 SAT 和 VAT 的全转录组基因表达水平。鉴定可能具有功能相关性的共表达基因模块，并将其与 BMI、血浆葡萄糖、胰岛素、HbA1c、甘油三酯、非酯化脂肪酸、丙氨酸氨基转移酶（ALAT）、天冬氨酸氨基转移酶（ASAT）、C 反应蛋白和 LDL-和 HDL 胆固醇水平进行相关性分析。

结果：在 SAT 和 VAT 中鉴定出的大约 70 个模块中，有三个 SAT 模块与血浆 HDL-胆固醇水平呈负相关，第四个模块与血浆葡萄糖和血浆甘油三酯水平呈负相关（p<5.33x10(-5)）。这些模块富含免疫和代谢基因。在 VAT 中，一个模块与 BMI 和胰岛素均相关，另一个模块与血浆葡萄糖相关（p<4.64x10(-5)）。该模块也富含炎症基因，并且与 SAT 中与 HDL 相关的模块在基因内容上具有明显的重叠。在 SAT 和 VAT 中鉴定出了一些差异表达的基因。

结论：在肥胖个体中，鉴定出与脂质和葡萄糖代谢参数相关的共表达基因群；这些基因富含免疫基因。确定了一些基因，其在 SAT 中的表达与血浆 HDL 胆固醇相关，而其在 VAT 中的表达与血浆葡萄糖相关。这突出了这些基因在脂质和葡萄糖代谢方面的重要性，以及这两个脂肪组织在这方面的具体作用。