Ylitalo Kati, Nuotio Ilpo, Viikari Jorma, Auwerx Johan, Vidal Hubert, Taskinen Marja-Riitta
Department of Medicine, Helsinki University Central Hospital, University of Helsinki, Haartmaninkatu 4, 00029 HYKS, Helsinki, Finland.
Metabolism. 2002 May;51(5):664-70. doi: 10.1053/meta.2002.32032.
This study aimed to assess the role of complement C3, hormone-sensitive lipase (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression in familial combined hyperlipidemia (FCHL). mRNA expression of these 3 determinants of adipose tissue fatty acid (FA) metabolism was quantified in subcutaneous adipose tissue of 41 Finnish FCHL patients and 14 normolipidemic control subjects. No difference in steady-state mRNA expression level of C3, HSL, or PPARgamma mRNA was detected between the FCHL patients and the control subjects. Adipose tissue C3 mRNA expression level correlated with the area under the curve (AUC) for glucose and for insulin in FCHL patients and control subjects. HSL mRNA level was positively correlated with waist-to-hip ratio in patients, whereas the correlation was negative in control subjects. A significant correlation was observed for PPARgamma with free FA (FFA)-AUC in the FCHL group, and an inverse correlation with serum triglycerides (TG) in the control subjects. Although no difference in adipose tissue gene expression of C3, HSL, or PPARgamma was observed between the FCHL patients and the control subjects, several significant correlations were observed between the mRNA levels and FCHL-related metabolic parameters. Thus, the genes of C3, HSL, and PPARgamma may exert a modifying effect on lipid and glucose metabolism in FCHL. However, defects in adipose tissue expression of these genes are not likely to play a primarily role in the pathogenesis of FCHL in Finnish FCHL families.
本研究旨在评估补体C3、激素敏感性脂肪酶(HSL)和过氧化物酶体增殖物激活受体γ(PPARγ)基因表达在家族性混合性高脂血症(FCHL)中的作用。对41名芬兰FCHL患者和14名血脂正常的对照者的皮下脂肪组织中这3种脂肪组织脂肪酸(FA)代谢决定因素的mRNA表达进行了定量分析。FCHL患者和对照者之间未检测到C3、HSL或PPARγ mRNA的稳态mRNA表达水平存在差异。FCHL患者和对照者的脂肪组织C3 mRNA表达水平与葡萄糖和胰岛素的曲线下面积(AUC)相关。患者的HSL mRNA水平与腰臀比呈正相关,而在对照者中呈负相关。在FCHL组中观察到PPARγ与游离脂肪酸(FFA)-AUC有显著相关性,在对照者中与血清甘油三酯(TG)呈负相关。尽管FCHL患者和对照者之间在脂肪组织C3、HSL或PPARγ的基因表达上未观察到差异,但在mRNA水平与FCHL相关代谢参数之间观察到了几个显著相关性。因此,C3、HSL和PPARγ基因可能对FCHL中的脂质和葡萄糖代谢产生调节作用。然而,在芬兰FCHL家族中,这些基因在脂肪组织中的表达缺陷不太可能在FCHL的发病机制中起主要作用。