Zabena Carina, González-Sánchez José L, Martínez-Larrad María T, Torres-García Antonio, Alvarez-Fernández-Represa Jesús, Corbatón-Anchuelo Arturo, Pérez-Barba Milagros, Serrano-Ríos Manuel
Department of Internal Medicine II, Hospital Clínico San Carlos, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Cea Bermúdez 66, 5 G., 28003, Madrid, Spain.
Obes Surg. 2009 Jan;19(1):87-95. doi: 10.1007/s11695-008-9727-0. Epub 2008 Oct 15.
Obesity has emerged as one of the most serious public health concerns in the twenty-first century. the fat mass and obesity associated gene (FTO) has been found to contribute to the risk of obesity in humans. Our aims in this study were to investigate the association of rs9939609 single nucleotide polymorphism (SNP) of the FTO gene with different obesity-related parameters, to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese and its correlations with other adipocytokine gene expressions.
The association between the rs9939609 FTO gene variant and obesity related parameters in 75 obese/morbidly obese adult patients and 180 subjects with body mass index (BMI) < 30 kg/m(2) (control group) was examined. Gene expression analyses: subcutaneous adipose tissue samples were obtained from 52 morbidly obese and five subjects with BMI < 30 kg/m(2). Visceral adipose tissue was also obtained from 35 morbidly obese patients. Weight, height, BMI, SBP, DBP, fasting glucose, lipid profile, proinsulin, insulin, leptin, and adiponectin (RIA) of patients were also obtained. Insulin resistance by HOMA(IR). rs9939609 of FTO genotyping using allele discrimination in real-time PCR. Genomic study of RNA extraction of adipose tissue and real-time PCR (RT-PCR) of adipocytokines and a housekeeping gene were quantified using TaqMan probes. Relative quantification was calculated using the DeltaDelta Ct formula.
The minor-(A) allele frequency of rs9939609 FTO gene in the whole population was 0.39. A strong association between this A allele and obesity was found, even after age-sex adjustment (p = 0.013). We found higher levels of FTO mRNA in subcutaneous adipose tissue from morbidly obese than in the control group (p = 0.021). FTO gene expression was lower in visceral than in subcutaneous adipose depot. However, this finding did not reach the level of statistical significance. A negative correlation between subcutaneous FTO gene expression and serum triglyceride levels and a positive correlation with leptin, perilipin, and visfatin gene expressions was found. In the visceral adipose tissue, these positive correlations were statistically significant only for perilipin.
Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients; (2) positive correlations between FTO mRNA and leptin, perilipin, and visfatin gene expressions in subcutaneous adipose tissue; (3) FTO and perilipin gene expressions were positively correlated in visceral fat depot. Overall these results may suggest a role of FTO in the regulation of lipolysis as well as in total body fat rather in fat distribution patterns.
肥胖已成为21世纪最严重的公共卫生问题之一。脂肪量和肥胖相关基因（FTO）已被发现会增加人类肥胖风险。本研究的目的是调查FTO基因rs9939609单核苷酸多态性（SNP）与不同肥胖相关参数之间的关联，评估病态肥胖患者皮下和内脏脂肪组织中FTO基因的表达及其与其他脂肪因子基因表达的相关性。
检测了75例肥胖/病态肥胖成年患者及180例体重指数（BMI）<30 kg/m²的受试者（对照组）中rs9939609 FTO基因变异与肥胖相关参数之间的关联。基因表达分析：从52例病态肥胖患者和5例BMI<30 kg/m²的受试者中获取皮下脂肪组织样本。还从35例病态肥胖患者中获取内脏脂肪组织。同时获取患者的体重、身高、BMI、收缩压、舒张压、空腹血糖、血脂谱、胰岛素原、胰岛素、瘦素和脂联素（放射免疫分析）。采用稳态模型评估胰岛素抵抗（HOMA-IR）。通过实时荧光定量PCR中的等位基因鉴别法对FTO基因进行rs9939609基因分型。使用TaqMan探针定量脂肪组织RNA提取以及脂肪因子和管家基因的实时荧光定量PCR（RT-PCR）。使用ΔΔCt公式计算相对定量。
整个人群中rs9939609 FTO基因的次要（A）等位基因频率为0.39。即使在进行年龄和性别调整后，也发现该A等位基因与肥胖之间存在强关联（p = 0.013）。我们发现病态肥胖患者皮下脂肪组织中FTO mRNA水平高于对照组（p = 0.021）。内脏脂肪组织中FTO基因表达低于皮下脂肪组织。然而，这一发现未达到统计学显著水平。发现皮下FTO基因表达与血清甘油三酯水平呈负相关，与瘦素、脂肪周蛋白和内脂素基因表达呈正相关。在内脏脂肪组织中，这些正相关仅在脂肪周蛋白方面具有统计学意义。
我们的结果表明：（1）西班牙病态肥胖成年患者中FTO基因变异的rs9939609 SNP与肥胖之间存在强关联；（2）皮下脂肪组织中FTO mRNA与瘦素、脂肪周蛋白和内脂素基因表达呈正相关；（3）内脏脂肪库中FTO和脂肪周蛋白基因表达呈正相关。总体而言，这些结果可能表明FTO在脂肪分解调节以及全身脂肪而非脂肪分布模式中发挥作用。
