CIC通过激活棕色脂肪组织逆转高脂膳食诱导的肥胖

CIC Reverses High-fat Diet Induced Obesity by Activating Brown Adipose Tissue

目的:探讨慢性间歇性冷暴露(Chronic intermittent cold exposure,CIC)干预对小鼠棕色脂肪组织的影响及其作用机制。方法:利用高脂饲料喂养C57BL/6小鼠,建立肥胖小鼠模型,同时给予CIC处理。将动物随机分为4组:对照组(Con组)、慢性间歇性冷暴露组(CIC组)、高脂组(HF组)、高脂冷暴露组(HF+CIC组),每组6只小鼠;CIC干预过程中,检测小鼠体重、肛温等数据。CIC处理16周后,麻醉处死小鼠取肩胛部位棕色脂肪组织,HE染色法观察棕色脂肪组织的形态学改变,Western blotting和q-PCR检测棕色脂肪组织Cirbp、PPAR-γ、C/EBPα、PGC-1α、UCP-1等信号分子表达情况。结果:肛温变化结果显示,干预初期小鼠冷暴露前后肛温差较大,冷适应后各组无显著性差异;与Con组相比,HF组小鼠体重升高、棕色脂肪占体重的比例下降,棕色脂肪组织中Cirbp、PPAR-γ、C/EBPα表达增高,PGC-1α、UCP-1表达下降(P<0.05);与HF组相比,HF+CIC组小鼠体重下降、棕色脂肪占体重的比例增高,棕色脂肪组织中Cirbp、PPAR-γ、C/EBPα表达下调,PGC-1α、UCP-1表达上调(P<0.05)。结论:CIC可能是通过激活Cirbp,影响PPAR-γ-PGC-1α-UCP-1信号通路的表达变化从而对棕色脂肪组织的活化产生影响,起到防治肥胖的作用。

Objective:To investigate the effect of chronic intermittent cold exposure(CIC)on brown adipose tissue in mice and its mechanism.Methods:C57BL/6 mice were fed with high fat diet to establish obese mice model,and then treated with CIC.The animals were randomly divided into four groups consisting of six animals each:control group(Con group),chronic intermittent cold exposure group(CIC group),high fat group(HF group),high fat and cold exposure group(HF+CIC group).During CIC intervention,the body weight and anal temperature of mice were measured.After 16 weeks of CIC treatment,the mice were sacrificed by anesthesia and the brown adipose tissue was taken from the scapular area.The morphological changes of brown adipose tissue were observed by HE staining.Western blotting and q-PCR were used to detect the expression of Cirbp,PPAR-,C/EBPα,PGC-lαand UCP-1 in brown adipose tissue.Results:The results of rectal temperature changes showed that the rectal temperature difference of mice before and after cold exposure was large in the early stage of intervention.There was no significant difference in rectal temperature after cold adaptation.Compared with Con group,the body weight of mice in HF group increased,the proportion of brown fat in body weight decreased,the expression of Cirbp,PPAR-and C/EBPαin brown adipose tissue increased,and the expression of PGC-1αand UCP-1 decreased(P<0.05).Compared with HF group,the body weight of mice in HF+CIC group decreased,the proportion of brown adipose tissue in body weight increased,the expression of Cirbp,PPAR-and C/EBPαin brown adipose tissue decreased,and the expression of PGC-1αand UCP-1 increased(P<0.05).Conclusion:CIC may affect the expression of PPAR--PGC-1α-UCP-1 signaling pathway by activating Cirbp,thus affecting the activation of brown adipose tissue and preventing obesity.