INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, Charles Merieux Lyon-Sud Medical School, Lyon, F-69003, France.
Obesity (Silver Spring). 2013 Jun;21(6):1165-73. doi: 10.1002/oby.20110.
The fat mass and obesity associated (FTO) gene is related to obesity, but the regulation of FTO expression in adipose tissue is not fully understood. We investigated FTO expression in paired subcutaneous and omental adipose tissues (SAT and OAT) from healthy women undergoing gynecological surgeries, and its relation with adiposity and insulin sensitivity.
FTO expression in SAT of type 2 diabetic patients treated or not with Rosiglitazone was also compared.
Both the mRNA and protein levels of FTO were higher in OAT from women than in SAT. Only OAT FTO protein levels negatively correlated with BMI and body fat mass, whereas SAT FTO mRNA levels were negatively correlated with subcutaneous fat deposition. In addition, SAT FTO mRNA and protein levels were increased in insulin resistant women (high HOMA) compared to insulin sensitive women (low HOMA), whereas OAT FTO expression was not different between these two subgroups. Interestingly, FTO mRNA levels were increased in SAT of type 2 diabetic patients, and treatment of diabetics with Rosiglitazone improved insulin sensitivity and reduced SAT FTO mRNA levels. Lastly, FTO expression was transiently increased in the early phase of 3T3-L1 cell differentiation, which coincides with the induction of PPARγ2 expression. However, partial reduction of FTO did not impact PPARγ2 expression and adipocyte differentiation.
Therefore, FTO gene expression is higher in OAT than in SAT in lean to moderately obese women. OAT FTO expression is associated with adiposity, whereas SAT FTO expression is associated with insulin sensitivity. These associations are independent of an effect of FTO on adipocyte differentiation.
肥胖相关基因（FTO）与肥胖有关，但脂肪组织中 FTO 表达的调控尚不完全清楚。我们研究了接受妇科手术的健康女性的皮下和网膜脂肪组织（SAT 和 OAT）中 FTO 的表达及其与肥胖和胰岛素敏感性的关系。
还比较了接受或不接受罗格列酮治疗的 2 型糖尿病患者 SAT 中 FTO 的表达。
OAT 中的 FTO mRNA 和蛋白水平均高于女性 SAT。只有 OAT 的 FTO 蛋白水平与 BMI 和体脂肪量呈负相关，而 SAT 的 FTO mRNA 水平与皮下脂肪沉积呈负相关。此外，与胰岛素敏感的女性（低 HOMA）相比，胰岛素抵抗的女性（高 HOMA）的 SAT FTO mRNA 和蛋白水平增加，而这两组之间 OAT 的 FTO 表达没有差异。有趣的是，2 型糖尿病患者的 SAT 中 FTO mRNA 水平增加，用罗格列酮治疗糖尿病可改善胰岛素敏感性并降低 SAT FTO mRNA 水平。最后，3T3-L1 细胞分化的早期阶段 FTO 表达短暂增加，与 PPARγ2 表达的诱导相吻合。然而，FTO 的部分减少并不影响 PPARγ2 的表达和脂肪细胞分化。
因此，在瘦至中度肥胖的女性中，OAT 中的 FTO 基因表达高于 SAT。OAT FTO 表达与肥胖有关，而 SAT FTO 表达与胰岛素敏感性有关。这些关联与 FTO 对脂肪细胞分化的影响无关。
