Baranova Ancha, Collantes Rochelle, Gowder Shobha J, Elariny Hazem, Schlauch Karen, Younoszai Abraham, King Steve, Randhawa Manpreet, Pusulury Sitapati, Alsheddi Tariq, Ong Janus P, Martin Lisa M, Chandhoke Vikas, Younossi Zobair M
Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, VA, USA.
Obes Surg. 2005 Jun-Jul;15(6):758-65. doi: 10.1381/0960892054222876.
This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis.
Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR.
A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers.
Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.
本研究调查人类脂肪组织中的表达模式,并鉴定可能参与异常能量稳态的基因。
前瞻性招募接受减肥手术的病态肥胖患者和非肥胖器官捐献者作为研究对象。在手术时从每个研究对象获取广泛的临床数据和内脏脂肪标本。选择50名肥胖患者和9名非肥胖对照进行进一步研究。用40,173个人类单个cDNA克隆制作了两组定制的双色cDNA微阵列。对每个样本进行微阵列实验,并用实时逆转录聚合酶链反应确认一组选定的基因表达值。
肥胖患者和非肥胖患者基因表达谱的比较确定了1208个在两组之间有统计学显著差异表达的基因。这些基因中最突出的是多个糖酵解酶编码基因;其他基因参与氧甾醇生物合成和信号传导,或是ATP结合转运蛋白和溶质载体。
病态肥胖患者脂肪组织中的差异基因表达包括与脂质和葡萄糖代谢、膜转运相关的基因,以及促进细胞周期的基因。这些发现是阐明肥胖分子发病机制和确定治疗干预潜在靶点的第一步。