目的 探讨温和的能量限制对小鼠脂代谢的影响.方法 给予3周龄C57BL/6小鼠高脂饮食12周后,按随机数字表法分组,对照组不限制饮食,实验组小鼠喂食对照组小鼠摄食量的85％,喂养12周后,收集小鼠血浆并冻存肝脏.抽提肝脏脂质并用酶法检测脂质含量,油红O染色观察肝脏的脂质沉积；用实时定量聚合酶链反应法检测肝脏脂肪代谢相关基因的表达；并测定LDL、TG分泌速率和小鼠原代肝细胞脂肪酸氧化速率.结果 实验组小鼠与对照组小鼠相比,在限食12周后:(1)体质量:(32.8±1.3)g比(38.9±3.5)g(P=0.007)；(2)血浆TG水平:(0.26±0.01) mmol/L比(0.41 ±0.02) mmol/L(P =0.02),肝脏内TG含量:(435.7±26.3)μg/mg蛋白质比(812.4±38.2)μg/mg蛋白质(P=0.001)；(3)实时定量聚合酶链反应结果显示,肝脏内长链脂肪酸和胆固醇合成相关基因mRNA表达水平无变化,但脂肪酸氧化基因mRNA表达水平显著增加(P=0.03).肝脏原代细胞内脂肪酸的氧化速度增加了53.1％±7.2％(P=0.01),血浆游离脂肪酸水平:(0.41±0.04)mmol/L比(0.62±0.02) mmol/L(P =0.04)；(4)肝脏中胆固醇:(85.2±9.8)μg/mg蛋白质比(169.3±13.5) μg/mg蛋白质(P=0.001),但血浆TC水平无显著改变.结论 长期温和的能量限制可以有效缓解高脂饮食引起的小鼠肝脏的脂肪变性,这与肝脏中游离脂肪酸的氧化速度升高及摄取量降低密切相关；同时降低了小鼠血浆TG的水平,但没有改变血浆TC水平.%Objective To determine the effect of chronic mild energy restriction on dyslipidemia induced by western type diet in C57BI/6 mice. Methods Thirty three-week-old C57BI/6 mice were randomly divided into two groups after being fed with western-type diet for 12 weeks. In control group,the mice were still fed with regular food and water. In the other group,mice were fed 15% less food intake for 12 weeks. The mice were anaesthetized during last day. Livers were harvested and hepatic lipids were measured by enzymatic methods and confirmed by oil-red 0 staining. The mRNA levels of hepatic lipid metabolism related genes were analyzed. Beta-oxidation in primary hepatocytes and hepatic very low density lipoprotein and triglyceride secretion rate were determined as well. Results After being fed 15% less food intake for 12 weeks,the body weights of C57BI/6 mice was gradually reduced from (38.9 ±3.5) g to (32. 8 ± 1. 3) g (P = 0.007) . The levels of plasma triglyceride,but not plasma cholesterol,was significantly decreased from (0. 41 ± 0. 02 ) mmol/L to ( 0.26 ± 0.01) mmol/L ( P = 0.02). Moreover,hepatic triglyceride content was significantly decreased from (812.4 ± 38.2) jig/mg protein to (435.7 ± 26.3) μg/mg protein (P =0. 001) ,which was partly associated the significantly enhanced hepatic free fatty acid bela-oxidation and gene levels. In addition,plasma free fatty acid levels were dropped one third as compared with that in control group (P = 0.04 ). Interestingly,hepatic cholesterol content,but not plasma cholesterol level was dramatically reduced from (169.3 ± 13.5 ) μg/mg protein to ( 85.2 ± 9. 8) μg/mg protein (P =0.001). Conclusions Chronic mild energy restriction significantly improves hepatic steatosis by increasing hepatic fatty acid beta-oxidation.
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