Upstream transcription factor-1 gene polymorphism is associated with increased adipocyte lipolysis
Upstream transcription factor-1 gene polymorphism is associated with increased adipocyte lipolysis
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DOI：
10.1210/jc.2005-0399
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发表时间：
2005-09-01
影响因子：
5.8
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Hoffstedt, J;Rydén, M;Arner, P
目的：个体间脂代谢的差异可能是由于遗传因素。描述了上游转录因子-1（USF-1）基因在usf 1 s1和usfs 2位点含有次要等位基因的单倍型的传递。我们调查这些多态性是否与脂肪细胞lipolysis.Methods和结果：共196名健康肥胖妇女进行了调查，在体外脂肪分解调节在SC脂肪细胞，这是在关系到usf 1基因中的usf 1 s1 C -> T和usf 1 s2 G -> A多态性。这两个多态性处于完全连锁不平衡。usf 1 s1/2 T/A等位基因与去甲肾上腺素（P = 0.005）、多巴酚丁胺（P = 0.008）、特布他林（P = 0.008）、CGP 12177（P = 0.015）和毛喉素（P = 0.006）的最大脂解作用增加相关。相比之下，没有显着的基因型效应的脂解敏感性（即半最大有效浓度）的任何药物被证明。对78名女性脂肪组织mRNA表达的分析显示，在肾上腺素受体后水平上调节脂解的基因中，T/ A基因型中蛋白激酶A亚基R1 α的水平增加（P = 0.02）。结论：usf 1基因的多态性与脂肪细胞中儿茶酚胺的脂解作用增加有关，这可能至少位于肾上腺素能受体后水平，涉及蛋白激酶A。
Objective: Variations in lipid metabolism between individuals could be due to genetic factors. A transmission of a haplotype of the upstream transcription factor-1 (USF-1) gene containing the minor alleles at the usf1s1 and usfs2 loci is described. We investigated whether these polymorphisms are associated with adipocyte lipolysis.Methods and Results: A total of 196 healthy obese women were investigated for in vitro lipolysis regulation in sc fat cells, which was set in relation to the usf1s1 C -> T and usf1s2 G -> A polymorphisms in the usf1 gene. The two polymorphisms were in complete linkage disequilibrium. The usf1s1/2T/A allele was associated with increases in the maximum lipolytic action of noradrenaline (P = 0.005), dobutamine ( P = 0.008), terbutaline (P = 0.008), CGP12177 (P = 0.015), and forskolin (P = 0.006). In contrast, no significant genotype effect on lipolytic sensitivity (i.e. half-maximum effective concentration) for any of the drugs was demonstrated. Analysis of adipose tissue mRNA expression in 78 women from genes regulating lipolysis at the post-adrenoceptor level showed an increased level of protein kinase A subunit R1 alpha in the T/ A genotype (P = 0.02).Conclusions: Polymorphism in the usf1 gene is associated with increased lipolytic effect of catecholamines in fat cells, which is localized at the postadrenoceptor level, possibly, at least, involving protein kinase A.