Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression
Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression
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DOI：
10.1074/jbc.m404569200
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发表时间：
2004-07-23
影响因子：
4.8
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Blüher, M;Patti, ME;Kahn, CR
具有脂肪特异性胰岛素受体敲除（FIRKO）的小鼠具有减少的脂肪组织质量，防止肥胖，并且具有延长的寿命。FIRKO小鼠的白色脂肪组织的特征还在于极化成两个主要的脂肪细胞群，一个小（< 50 μ m）和一个大（> 100 μ m），其在基础甘油三酯合成和脂解方面不同，以及在脂肪酸合成酶、固醇调节元件结合蛋白1c和CCAAT/增强子结合蛋白α（C/EBP-α）的表达方面不同。使用从FIRKO和对照（IR lox/lox）小鼠的大脂肪细胞和小脂肪细胞分离的RNA在寡核苷酸微阵列上进行基因表达分析。在所示的12，488个基因/表达序列标签中，111个基因在四个脂肪细胞群体中以p < 0.001水平差异表达。这些变化表现出10个定义的模式，并发生在两个不同的调节作用。63个基因被鉴定为主要取决于脂肪细胞大小的表达变化，包括C/EBP-α、C/EBP-δ、超氧化物歧化酶3和血小板衍生生长因子受体。48个基因主要受胰岛素信号传导障碍的调节，包括转化生长因子β、干扰素γ、胰岛素样生长因子I受体、激活转录因子3、醛脱氢酶2和蛋白激酶C δ。这些数据表明，脂肪细胞的内在异质性与脂肪细胞大小和胰岛素信号相关的基因表达的差异。
Mice with a fat-specific insulin receptor knock-out (FIRKO) have reduced adipose tissue mass, are protected against obesity, and have an extended life span. White adipose tissue of FIRKO mice is also characterized by a polarization into two major populations of adipocytes, one small (< 50 mu m) and one large (> 100 mum), which differ with regard to basal triglyceride synthesis and lipolysis, as well as in the expression of fatty acid synthase, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding protein alpha (C/EBP-alpha). Gene expression analysis using RNA isolated from large and small adipocytes of FIRKO and control (IR lox/lox) mice was performed on oligonucleotide microarrays. Of the 12,488 genes/expressed sequence tags represented, 111 genes were expressed differentially in the four populations of adipocytes at the p < 0.001 level. These alterations exhibited 10 defined patterns and occurred in response to two distinct regulatory effects. 63 genes were identified as changed in expression depending primarily upon adipocyte size, including C/EBP-alpha, C/EBP-delta, superoxide dismutase 3, and the platelet-derived growth factor receptor. 48 genes were regulated primarily by impairment of insulin signaling, including transforming growth factor beta, interferon gamma, insulin-like growth factor I receptor, activating transcription factor 3, aldehyde dehydrogenase 2, and protein kinase C delta. These data suggest an intrinsic heterogeneity of adipocytes with differences in gene expression related to adipocyte size and insulin signaling.