长期温和的能量限制改善C57BL/6小鼠高脂喂养后的脂代谢紊乱  

Chronic mild energy restriction improves dyslipidemia in C57BL/6 mice fed with western type diet

作　　者：李国平[1] 唐蔚青[1] 李红霞[1] 满永[1] 黎健[1] 陈保生[2] 

机构地区：[1]卫生部北京医院 卫生部北京老年医学研究所 卫生部老年医学重点实验室,100730 [2]中国医学科学院基础医学研究所 中国协和医科大学基础医学院医学分子生物学国家重点实验室

出　　处：《中国心血管杂志》2012年第2期124-127,共4页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金(30872712;81070634;81170381);国家重点基础研究发展计划(973计划)课题(2012CB517502)~~

摘　　要：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 C57BIJ6 mice. Methods Thirty three-week-old C57B1/6 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 O 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 C57BL/6 mice was gradually reduced from （38.9 ±3.5 ） g to （52. 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 ） μg/mg protein to （435.7± 26. 5 ）μg/mg protein （ P = 0. 001 ）, which was partly associated the significantly enhanced hepatic free fatty acid beta-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.

关 键 词：能量限制 脂代谢 脂肪酸氧化速率 

分 类 号：R589.2[医药卫生—内分泌]