Moon Jae Hoon, Kim Hyung Jun, Kim Hyun Min, Choi Sung Hee, Lim Soo, Park Young Joo, Jang Hak Chul, Cha Bong Soo
1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seoul National University College of Medicine, Kyunggi-do, Korea.
Thyroid. 2013 Sep;23(9):1057-65. doi: 10.1089/thy.2012.0457. Epub 2013 Aug 28.
The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins. In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of 3,3',5-triiodo-L-thyronine (T3) treatment on hepatic LRP1 expression.
C57BL/6 mice were fed a normal diet (control group) or a low-iodine diet supplemented with 0.15% propylthiouracil (PTU/LI group) for 4 weeks. Mice in the PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 μg/kg of body weight) for 7 days. HepG2 cells were incubated in fetal bovine serum or charcoal-stripped fetal bovine serum with various concentrations of T3. The expression and function of LRP1 in liver samples and cells were analyzed.
Hypothyroidism was successfully induced in PTU/LI mice. Hepatic LRP1 protein expression was lower in the PTU/LI group than in the control group. T3 treatment upregulated hepatic LRP1 protein expression in PTU/LI mice. LRP1 expression in HepG2 cells was reduced after incubation in the medium containing charcoal-stripped fetal bovine serum, which mimics hypothyroidism in vitro, and was recovered by T3 treatment. The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2.0 nM T3. However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or in HepG2 cells. T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1.
Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by the thyroid hormone. These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.
甲状腺功能减退对脂质代谢的致动脉粥样硬化作用可能部分源于残余脂蛋白清除率降低。在本研究中，我们调查了甲状腺功能减退时肝脏低密度脂蛋白受体相关蛋白1（LRP1，一种残余脂蛋白受体）的表达情况，以及3,3',5-三碘-L-甲状腺原氨酸（T3）治疗对肝脏LRP1表达的影响。
将C57BL/6小鼠分为正常饮食组（对照组）或喂食含0.15%丙硫氧嘧啶的低碘饮食组（PTU/LI组），持续4周。PTU/LI组小鼠腹腔注射T3（0、30和150μg/kg体重），持续7天。将HepG2细胞在含有不同浓度T3的胎牛血清或经活性炭处理的胎牛血清中培养。分析肝脏样本和细胞中LRP1的表达及功能。
PTU/LI小鼠成功诱导出甲状腺功能减退。PTU/LI组肝脏LRP1蛋白表达低于对照组。T3治疗上调了PTU/LI小鼠肝脏LRP1蛋白表达。在模拟甲状腺功能减退的经活性炭处理的胎牛血清培养基中培养后，HepG2细胞中LRP1表达降低，而T3治疗可使其恢复。T3治疗以剂量依赖方式增加HepG2细胞中LRP1蛋白表达，直至T3浓度达到2.0nM。然而，在肝脏样本或HepG2细胞中，甲状腺功能减退状态或T3治疗均不影响LRP1 mRNA转录。T3对HepG2细胞的治疗增加了细胞通过LRP1对脂质结合载脂蛋白E的摄取。
