Carlsson E, Johansson L E, Ström K, Hoffstedt J, Groop L, Holm C, Ridderstråle M
Department of Clinical Sciences, Diabetes and Endocrinology, Malmö University Hospital, Lund University, Sweden.
Int J Obes (Lond). 2006 Sep;30(9):1442-8. doi: 10.1038/sj.ijo.0803299. Epub 2006 Mar 14.
Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes.
We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects.
We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects.
The HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects.
激素敏感性脂肪酶（HSL）是脂肪细胞中甘油三酯储存库动员脂肪酸的关键酶。本研究旨在探讨HSL基因启动子变体C-60G（一种先前在体外与启动子活性降低相关的多态性）在肥胖症和2型糖尿病中的作用。
我们对两组材料进行了基因分型，一组由肥胖受试者和非肥胖对照组成，一组是后代-父母三人组，其中后代腹部肥胖，另一组三人组中，后代患有2型糖尿病或葡萄糖稳态受损。构建了含HSL C-60G G等位基因的HSL启动子，并在HeLa细胞和原代大鼠脂肪细胞中与含C等位基因的构建体进行比较测试。对33名肥胖受试者的皮下和内脏脂肪中的HSL mRNA水平进行了定量分析。
我们发现，在瘦对照组中，常见的C等位基因与腰围增加和腰臀比升高有关，但肥胖与非肥胖受试者之间的基因型频率没有差异。C等位基因向腹部肥胖后代的传递显著增加，但未观察到C等位基因向葡萄糖稳态受损后代的传递增加。G等位基因在HeLa细胞和原代大鼠脂肪细胞中的转录减少。肥胖受试者皮下脂肪中的HSL mRNA水平显著高于内脏脂肪。
HSL C-60G多态性与非肥胖受试者腰围增加有关。
