Bendlová B, Vejražková D, Včelák J, Lukášová P, Burkoňová D, Kunešová M, Vrbíková J, Dvoráková K, Vondra K, Vanková M
Institute of Endocrinology, Prague, Czech Republic.
Physiol Res. 2008;57 Suppl 1:S77-S90. doi: 10.33549/physiolres.931492. Epub 2008 Feb 13.
Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.
游离脂肪酸（FFA）是PPARγ2受体的天然配体。FFA的血浆浓度和组成可能是导致关于Pro12Ala对体重指数（BMI）、胰岛素敏感性或2型糖尿病（DM2）易感性影响的结论存在高度异质性的因素之一。我们的目的是研究324名无糖尿病的瘦人（男/女：99/225；年龄32±11岁；BMI 23.9±4.0kg/m²）中Pro12Ala多态性与FFA状态、代谢标志物和身体组成之间的关系及可能的相互作用，这些受试者有或无DM2家族史。DM2家族史与较低的多不饱和脂肪酸（PUFA）百分比和略高的单不饱和脂肪酸（MUFA）百分比相关。在受试人群中，Pro12Ala多态性的存在与空腹血浆FFA浓度或组成、葡萄糖和脂质代谢的人体测量或代谢标志物无关。然而，携带状态与FFA水平的相互作用影响基础血糖水平、胰岛素敏感性和处置指数、甘油三酯、高密度脂蛋白胆固醇和瘦素水平，尤其是在女性中。12Ala携带者的代谢效应受FFA水平影响——仅在血浆FFA浓度低时才可见12Ala的有益作用。令人惊讶的是，高PUFA/SFA比值与较低的胰岛素敏感性相关，12Ala等位基因的保护作用在有DM2家族史的受试者中明显。基于我们的研究结果和已发表的数据，我们建议在使用噻唑烷二酮类药物治疗前对糖尿病患者进行PPARγ2基因Pro12Ala多态性的基因分型，并就调节代谢结果的饮食和体育活动对受试者进行教育。
