MRI脂质定量评估Irisin干预后小鼠肩胛间棕色脂肪激活

MRI quantitative lipid content for assessment activation of interscapular brown adipose tissue in mice after Irisin intervention

目的探讨MR化学位移选择成像活体定量评估Irisin干预后小鼠肩胛间棕色脂肪组织(iBAT)脂质含量与其活性的相关性。方法以12只小鼠构建高脂饮食(HFD)诱导肥胖模型(HFD组),随机将其分为磷酸盐缓冲液(PBS)亚组(HFD PBS亚组)、Irisin干预2周亚组(HFD Irisin2w亚组)及干预4周亚组(HFD Irisin4w亚组),每亚组4只;另以正常饮食(CD)饲养4只小鼠(CD组)。对各组对应注射PBS或Irisin溶液予以干预4周后行7.0T Micro MR化学位移成像,测量小鼠iBAT脂质含量MRI;以HE染色测量iBAT细胞内脂滴面积和脂质含量HE,以免疫组织化学法检测iBAT解耦联蛋白1(UCP-1)表达水平。比较各指标组(亚组)间差异,评价MR化学位移成像定量小鼠iBAT脂质含量MRI与病理学检测结果的相关性。结果HFD PBS亚组小鼠iBAT脂质含量MRI、脂滴面积及脂质含量HE均大于CD组小鼠(P均<0.05),而UCP-1表达水平低于CD组(P<0.05)。HFD Irisin2w亚组小鼠iBAT脂质含量HE低于、而UCP-1表达水平高于HFD PBS亚组小鼠(P均<0.05)。HFD Irisin4w亚组iBAT脂质含量MRI及脂质含量HE显著低于HFD PBS亚组、HFD Irisin2w亚组(P均<0.05),脂滴面积明显小于HFD Irisin2w亚组(P<0.05),UCP-1表达水平高于HFD PBS亚组(P<0.05)。小鼠iBAT脂质含量MRI与通过组织病理学测定的iBAT脂滴面积及脂质含量HE呈正相关(r=0.750、0.974,P均<0.05),与UCP-1表达水平呈负相关(r=-0.681,P=0.01)。结论Irisin可激活HFD小鼠iBAT活性;MR化学位移选择成像定量小鼠iBAT脂质含量与组织病理学iBAT活性具有相关性。

Objective To investigate the correlation between the lipid content quantified with MR chemical shift-selective imaging and the activity of interscapular brown adipose tissue(iBAT)in mice after Irisin intervention.Methods Twelve high-fat diet(HFD)induced obese mice(HFD group)were equally assigned to phosphate buffer solution(PBS)subgroup(HFD PBS subgroup),2 weeks Irisin intervention subgroup(HFD Irisin2w subgroup)and 4 weeks Irisin intervention subgroup(HFD Irisin4w subgroup),respectively(each n=4),while normal control diet(CD)mice were assigned to CD group(n=4).The mice were intraperitoneally injected with PBS or Irisin solution for 4 weeks,respectively.7.0T Micro MR chemical shift-selective imaging was used to measure lipid content MRI of iBAT.HE staining was used to measure the area of lipid droplets and lipid content HE in brown adipocytes,and the expression level of uncoupling protein-1(UCP-1)in iBAT was explored with immunohistochemistry.Then the above indexes were compared between group/subgroups,and the correlations of lipid content MRI detected with MR chemical shift-selective imaging and the pathological indicators were assessed.Results The lipid content MRI,lipid area and lipid content HE of iBAT in HFD PBS group were higher than those in CD group(all P<0.05),while the expression levels of UCP-1 was lower than that in CD group(P<0.05).The lipid content HE in HFD Irisin2w subgroup was lower than that in HFD PBS subgroup(P<0.05),while the expression level of UCP-1 was higher than that in HFD PBS subgroup(P<0.05).The lipid content MRI and the lipid content HE of iBAT were significantly lower in HFD Irisin4w subgroup than those in HFD PBS and HFD Irisin2w subgroup(all P<0.05),and the lipid area in HFD Irisin4w subgroup was smaller than that in HFD Irisin2w subgroup(P<0.05),the expression level of UCP-1 in HFD Irisin4w was higher than that in HFD PBS subgroup(P<0.05).The quantity of iBAT lipid content MRI was positive correlated with iBAT lipid droplet area and lipid content HE measured histopathologically(r=0.750,0.974,both P<0.05)and negative correlated with the expression level of UCP-1(r=-0.681,P=0.01).Conclusion Irisin could activate iBAT activity in HFD mice.The lipid content of iBAT quantified by MR chemical shift-selective imaging was correlated with the iBAT activity assessed histopathologically in mice.