冷刺激对小鼠脂肪组织褐色化和脂代谢的影响

The Effect of Cold Stimulation on Fat Tissue Browning and Lipid Metabolism in Mice

目的:探讨4摄氏度冷刺激对小鼠脂肪组织褐色化的影响。方法:野生型小鼠在4摄氏度环境下饲养一周,称取小鼠重量并取不同的脂肪组织固定,进行H&E染色;对血液中甘油三酯、脂肪酸的水平进行检测;检测不同脂肪组织中脂肪含量和相关蛋白的表达水平。结果:野生型小鼠在4℃环境下饲养一周后体重明显降低。血液中甘油三酯、脂肪酸和甘油的水平明显下降。皮下白色脂肪组织(subcutaneous white adipose tissue, SWAT),腹腔生殖腺旁白色脂肪(gonadal visceral white adipose tissue, GWAT)和褐色脂肪(brown adipose tissue, BAT)中的脂肪含量明显降低,其中SWAT和BAT中脂肪含量降低近50%。SWAT发生明显的褐色化现象,组织中出现含有多个脂滴的脂肪细胞,同时褐色化的标志蛋白UCP1(uncoupling protein 1)和Cidea明显增加。GWAT中脂滴仍呈现单室大脂滴,脂肪细胞变小,脂肪积累降低约14%,低于SWAT和BAT中的相应变化。BAT组织中脂滴明显变小,UCP1的表达明显增加。同时我们在三种脂肪组织中都观察到线粒体相关蛋白CPT1 (Carnitine palmitoyltransferase I)的明显增加。结论:冷刺激能明显改变小鼠的脂代谢状态,全身的脂肪积累明显降低。SWAT发生明显的褐色化现象,Cidea和UCP1的表达明显增加。SWAT, GWAT和BAT脂肪组织中有明显的线粒体活性的增加。

Objective:Here,we wanted to investigate the role of cold stimulation in regulating fat tissue browning and whole body lipid metabolism in mice.Methods:The mice were maintained at 4℃for 1 week.Mice body weight was measured.Fat tissues were collected and fixed for H&E staining.Serum levels of TAG,FFA and glycerol were measured.Fat tissue TAG content and protein expression profile were analyzed.Results:Compared to control mice,the body weight of mice was reduced after cold-stimulation for 1 week.The serum levels of triglyceride,free fatty acids and glycerol were decreased.The TAG contents in SWAT(subcutaneous white adipose tissue),GWAT(gonadal visceral white adipose tissue)and BAT(brown adipose tissue)were dramatically reduced in cold-stimulated mice,especially nearly 50%reduction in SWAT and BAT.Browning phenotype was observed in SWAT of cold-stimulated mice with the appearance of adipocytes with multilocular lipid droplets and high expression of UCP1(uncoupling protein 1)and Cidea.Lipid droplets in GWAT were still unilocular under cold stimulation.The size of lipid droplet was reduced in GWAT with 14%reduction in TAG content under cold stimulation.The expression of UCP1 and Cidea was not significant induced in GWAT,indicating that browning did not occur in GWAT.The BAT of cold-stimulated mice had smaller lipid droplets and higher expression of UCP1.Higher expression of CPT1(Carnitine palmitoyltransferase I)in SWAT,GWAT and BAT of cold-stimulated mice was observed.Conclusion:Cold stimulation could dramatically affect the lipid metabolism status of mice.Whole body fat accumulation was dramatically reduced in cold-stimulated mice.Browning occurred in SWAT with the induction expression of UCP1 and Cidea.All fat tissue showed elevated expression of CPT1,a mitochondrial related protein.