Mutch David M, Tordjman Joan, Pelloux Véronique, Hanczar Blaise, Henegar Corneliu, Poitou Christine, Veyrie Nicolas, Zucker Jean-Daniel, Clément Karine
INSERM, Nutriomique U872 Team 7, Paris, France.
Am J Clin Nutr. 2009 Jan;89(1):51-7. doi: 10.3945/ajcn.2008.26802. Epub 2008 Dec 3.
Adipose tissue gene expression analysis in humans now provides a tremendous means to discover the physiopathologic gene targets critical for our understanding and treatment of obesity. Clinical studies are emerging in which adipose gene expression has been examined in hundreds of subjects, and it will be fundamentally important that these studies can be compared so that a common consensus can be reached and new therapeutic targets for obesity proposed.
We studied the effect of the biopsy sampling methods (needle-aspirated and surgical) used in clinical investigation programs on the functional interpretation of adipose tissue gene expression profiles.
A comparative microarray analysis of the different subcutaneous adipose tissue sampling methods was performed in age-matched lean (n = 19) and obese (n = 18) female subjects. Appropriate statistical (principal components analysis) and bioinformatic (FunNet) functional enrichment software were used to evaluate data. The morphology of adipose tissue samples obtained by needle-aspiration and surgical methods was examined by immunohistochemistry.
Biopsy techniques influence the gene expression underlying the biological themes currently discussed in obesity (eg, inflammation, extracellular matrix, and metabolism). Immunohistochemistry experiments showed that the easier to obtain needle-aspirated biopsies poorly aspirate the fibrotic fraction of subcutaneous adipose tissue, resulting in an underrepresentation of the stroma-vascular fraction.
The adipose tissue biopsy technique is an important caveat to consider when designing, interpreting, and, most important, comparing microarray experiments. These results will have crucial implications for the clinical and physiopathologic understanding of human obesity and therapeutic approaches.
目前，人类脂肪组织基因表达分析为发现对我们理解和治疗肥胖症至关重要的生理病理基因靶点提供了一种强大的手段。越来越多的临床研究对数百名受试者的脂肪基因表达进行了检测，能够对这些研究进行比较从而达成共识并提出肥胖症新的治疗靶点至关重要。
我们研究了临床研究项目中使用的活检采样方法（针吸活检和手术活检）对脂肪组织基因表达谱功能解读的影响。
对年龄匹配的瘦女性（n = 19）和肥胖女性（n = 18）受试者的不同皮下脂肪组织采样方法进行了比较性微阵列分析。使用了适当的统计方法（主成分分析）和生物信息学方法（FunNet）功能富集软件来评估数据。通过免疫组织化学检查针吸活检和手术方法获得的脂肪组织样本的形态。
活检技术会影响肥胖症当前所讨论的生物学主题（如炎症、细胞外基质和代谢）相关的基因表达。免疫组织化学实验表明，更容易获取的针吸活检样本难以吸出皮下脂肪组织的纤维化部分，导致基质血管部分代表性不足。
在设计、解读以及最重要的是比较微阵列实验时，脂肪组织活检技术是一个需要考虑的重要注意事项。这些结果将对人类肥胖症的临床和生理病理理解以及治疗方法产生关键影响。
