BMI匹配的糖耐量正常的胰岛素敏感个体和胰岛素抵抗个体皮下脂肪和肌肉全基因表达谱

1.      Global Gene Expression Profiles of Subcutaneous Adipose and Muscle From Glucose-Tolerant, Insulin-Sensitive, and Insulin-Resistant Individuals Matched for BMI

BMI匹配的糖耐量正常的胰岛素敏感个体和胰岛素抵抗个体皮下脂肪和肌肉全基因表达谱海南医学院附属医院内分泌科王新军

Abstract

OBJECTIVE To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI.

 

目的  观察与BMI匹配的非糖尿病胰岛素抵抗个体相比，胰岛素敏感个体皮下脂肪和骨骼肌基因表达谱的变化。

RESEARCH DESIGN AND METHODS A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis.

研究设计和方法  共选择了极端的胰岛素敏感性的62例非糖尿病个体（31例胰岛素抵抗和31例胰岛素敏感者；其中40例为欧洲和美国人，22例为非裔美国人），其年龄和肥胖指标匹配。测定其全基因表达谱，利用基因表达富集分析法比较不同种族之间、胰岛素抵抗和胰岛素敏感者之间的基因表达谱差异。

 RESULTS African American and European-American subjects differed in 58 muscle and 140 adipose genes, including many inflammatory and metabolically important genes. Peroxisome proliferator?activated receptor γ cofactor 1A (PPARGC1A) was 1.75-fold reduced with insulin resistance in muscle, and fatty acid and lipid metabolism and oxidoreductase activity also were downregulated. Unexpected categories included ubiquitination, citrullination, and protein degradation. In adipose, highly represented categories included lipid and fatty acid metabolism, insulin action, and cell-cycle regulation. Inflammatory genes were increased in European-American subjects and were among the top Kyoto Encyclopedia of Genes and Genomes pathways on gene-set enrichment analysis. FADS1, VEGFA, PTPN3, KLF15, PER3, STEAP4, and AGTR1 were among genes expressed differentially in both adipose and muscle.

结果  非裔美国人和欧美人有58个肌肉基因和140个脂肪基因存在差异，其中包括许多炎症和代谢的重要基因。过氧化物酶体增殖物激活受体γ辅助因子1A（PPARGC1A）在胰岛素抵抗个体肌肉降低1.75倍，脂肪酸和脂质代谢和氧化还原酶的活性也存在下调。出乎意料的是，包括泛素化、瓜氨酸和蛋白质的降解等基因也存在差异。在脂肪中，具有代表性的基因类别包括脂质和脂肪酸代谢、胰岛素作用和细胞周期调控。基因表达富集分析显示炎症基因在欧美个体增加，在京都基因与基因组百科全书中居高水平。脂肪和肌肉中基因表达均存在差异的基因包括FADS1、VEGFA、PTPN3、KLF15、PER3、STEAP4和AGTR1。

CONCLUSIONS Adipose tissue gene expression showed more differences between insulin-resistant versus insulin-sensitive groups than the expression of genes in muscle. We confirm the role of PPARGC1A in muscle and show some support for inflammation in adipose from European-American subjects but find prominent roles for lipid metabolism in insulin sensitivity independent of obesity in both tissues.

结论  在胰岛素抵抗和胰岛素敏感组，脂肪组织比肌肉的基因表达存在更多差异。我们确认了PPARGC1A在肌肉中的作用，并显示在在欧美个体脂肪的炎症中的一些支持性证据，但发现在脂肪及肌肉这两种组织中，胰岛素敏感性脂质代谢方面具有突出作用，这种作用不依赖于肥胖。