高脂食物诱导的肥胖小鼠不同脑区即刻早期蛋白和酪氨酸羟化酶的变化

Immediate-early c-fos and tyrosine hydroxylase protein expression in different brain regions in high-fat induced obesity in mice

目的:在高脂食物诱导肥胖的小鼠中检测多巴胺神经元的表达。方法:10只雄性小鼠饲喂高脂膳食作为高脂食物组(HFD),10只雄性小鼠饲喂10%脂肪膳食作为对照组(NCD)。实验第10周,小鼠禁食12 h后称重,尾静脉取血测定基础血糖水平;实验11周进行葡萄糖耐受(GTT)测试和胰岛素抵抗实验(ITT);实验12周,动物禁食4 h后处死,测定血清胰岛素和瘦素(leptin)浓度,免疫组织化学法检测即刻早期蛋白(c-Fos-ir)和酪氨酸羟化酶(TH-ir)的表达。结果:饲喂12周高脂食物后,HFD组体重明显增加。GTT测试显示HFD组在15 min和30min血糖浓度均明显高于NCD组(P<0.05)。ITT测试显示HFD组在15 min和30 min血糖浓度均显著高于NCD组(P<0.05)。同时,禁食后,HFD组的胰岛素浓度和leptin浓度显著高于NCD组(P<0.01)。免疫组化结果表明HFD组在伏隔核、下丘脑室旁核、腹侧背盖区和黑质的c-Fos-ir细胞数均明显多于NCD组(P<0.01),且腹侧被盖区和黑质的TH-ir和共表达TH/Fos-ir细胞也显著多于NCD组(P<0.01)。而且HFD组VTA区和SN区TH-ir的细胞数与HFD组小鼠的终体重呈正相关(P<0.05)。结论:长期饲喂高脂食物导致的肥胖与奖赏系统多巴胺神经元的可塑性有关。

Objective： To examine brain dopmnine expression in chronic high-fat diet（ HFD）-induced obese mice. Methods： Ten male mice were fed by a high-fat diet （HF： 45% of ealories from fat） tbr 12 weeks and then classified as HFD group. Ten male mice wer fed a low-fat diet （LF： 10% of calories from fat） and used as control group （NCD）. In the 10Lh week, the blood of the caudal vein was colleeted to determine the basal blood glueose level after both groups mice were fast for 12 h. Intrapelitoneal （IP） glueose tolerance test （GTF） and insulin tolerance （1TF） were performed in HFD and NCD mice in the 12th week. Animals were sacrilic, ed after fasting for 4 hours at the 12th week. Brain tissues were processed tbr Fos-ir and TH-ir by immunohistochemistry. Results： Atter 12 weeks of feeding, body weight was significant higher in HFD mice than flint in NCD ones. During GTT and ITT, HFD mice had significantly deereased glueose tolerance and insulin toler- ance at 15 min and 30 min respectively than NCD ones （P 〈 0.05）. There were higher plasma insulin concentration and leptin concentration in HFD mice than those in NCD ones （ P 〈 0.05）. High fat-induced increased body weight was associated with increased cellular activation, indicated by Fos immunoreaetive （ir） staining, in nucleus aeeumbens（ NAee）, paraventricular nucleus （PVN）, ventral tegmental area （VTA） and sul）stantia nigra （SN） than those of NCD ones （ P 〈 0.05 ） ; and ＇also significantly assoeiated with enhanced in the number of cells labeled for tyrosine hydroxylase （TH-ir）, and the numboer of cells co-labeled for TH-ir/Fos-ir in the VTA and SN than those of NCD ones （ P 〈 0. 01 ）. Moreover, there was significantly relationship TH-ir positive cell numbers with final body weight in VTA and SN in HID mice （ P 〈 0. 05）. Conclusion： The results showed that chronic consumption of high-fat tbod was associated with plasticity-related changes in reward eircuit-