Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice
Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice
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DOI：
10.1111/j.1478-3231.2010.02361.x
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发表时间：
2011-01-01
影响因子：
6.7
通讯作者：
Nervi, Flavio
中科院分区：
文献类型：
--
作者：
Amigo, Ludwig;Husche, Constanze;Nervi, Flavio
背景与目的：胆囊切除术（XGB）后胆汁酸（BA）池大小保持不变，但其循环速度加快，使肠肝系统暴露于增加的BA通量。甘油三酯（TG）和BA代谢在功能上是相互关联的。我们研究了胆囊（GB）消融是否会改变肝脏TG代谢。方法：对雄性小鼠进行XGB注射，饲喂正常饮食。在一些实验中，小鼠接受1%烟酸饮食以阻止脂肪分解。XGB后1-2个月测定BA、TG代谢参数及微粒体甘油三酯转移蛋白（MTTP）活性。测定血清参数、肝脏脂质及脂代谢相关基因mRNA表达量。结果：XGB小鼠胆BA池大小和合成正常，但在白天光照期胆BA分泌增加一倍。血清和肝脏TG浓度升高25% (P < 0.02)，肝脏极低密度脂蛋白(VLDL)-TG和apoB-48产量分别升高15% （P < 0.03）和50% （P < 0.01）。饲喂1%的烟酸确实使VLDL的生成正常化。XGB后MTTP活性增加15% （P < 0.005）。XGD小鼠肝脏游离脂肪酸（FFA）合成、含量及脂质代谢相关基因mRNA水平维持正常。结论：XGB使血清和肝脏TG水平升高，VLDL产量增加，经烟酸处理后恢复正常。结果表明，XGB小鼠脂肪组织向肝脏的游离脂肪酸通量增加。他们支持这样的假设，即GB在调节肝脏TG代谢中起作用，并且XGB可能有利于肝脏中脂肪的积累。
Background & aims: Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism. Methods: Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined. Results: BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P < 0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P < 0.03) and 50% (P < 0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P < 0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice. Conclusions: XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver.