Adamo Kristi B, Dent Robert, Langefeld Carl D, Cox Miranda, Williams Kathryn, Carrick Kevin M, Stuart Joan S, Sundseth Scott S, Harper Mary-Ellen, McPherson Ruth, Tesson Frédérique
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Obesity (Silver Spring). 2007 May;15(5):1068-75. doi: 10.1038/oby.2007.630.
Peroxisome proliferator-activated receptor gamma (PPARgamma) and its response gene, Acyl CoA synthetase 5 (ACSL5), which has an important role in fatty acid metabolism, may affect weight loss in response to caloric restriction. Therefore, we aimed to determine whether these genes were involved in the interindividual response to dietary treatment. Genotypic/phenotypic comparisons were made between selected obese women from the quintiles losing the most (diet responsive, n = 74) and the quintiles losing the least (diet-resistant, n = 67) weight in the first 6 weeks of a 900-kcal formula diet. Two common PPARgamma single nucleotide polymorphisms, Pro(12)Ala and C1431T, and eight polymorphisms across the ACSL5 gene were selected for single locus and haplotypic association analyses. The PPARgamma Pro(12)Ala single nucleotide polymorphism was associated with diet resistance (odds ratio = 3.48, 95% confidence interval = 1.41 to 8.56, p = 0.03), and the rs2419621, located in the 5'untranslated region of the ACSL5 gene, displayed the strongest association with diet response (odds ratio = 3.45, 95% confidence interval = 1.61 to 7.69, p = 0.001). Skeletal muscle ACSL5 mRNA expression was significantly lower in carriers of the wildtype compared with the variant rs2419621 allele (p = 0.03). Our results suggest a link between PPARgamma2 and ACSL5 genotype and diet responsiveness.
过氧化物酶体增殖物激活受体γ（PPARγ）及其反应基因酰基辅酶A合成酶5（ACSL5）在脂肪酸代谢中起重要作用，可能影响热量限制后的体重减轻。因此，我们旨在确定这些基因是否参与个体对饮食治疗的反应。在900千卡配方饮食的前6周，对体重减轻最多的五分位数（饮食反应者，n = 74）和体重减轻最少的五分位数（饮食抵抗者，n = 67）中挑选出的肥胖女性进行基因型/表型比较。选择两个常见的PPARγ单核苷酸多态性Pro(12)Ala和C1431T，以及ACSL5基因上的八个多态性进行单基因座和单倍型关联分析。PPARγ Pro(12)Ala单核苷酸多态性与饮食抵抗相关（优势比 = 3.48，95%置信区间 = 1.41至8.56，p = 0.03），位于ACSL5基因5'非翻译区的rs2419621与饮食反应的关联最强（优势比 = 3.45，95%置信区间 = 1.61至7.69，p = 0.001）。与rs2419621变异等位基因携带者相比，野生型携带者的骨骼肌ACSL5 mRNA表达显著降低（p = 0.03）。我们的结果表明PPARγ2和ACSL5基因型与饮食反应性之间存在联系。
