β-石竹烯通过上调PPARγ/PGC-1α/UCP1通路促进肥胖小鼠白色脂肪棕色化作用  

β-caryophyllene promotes white fat browning in obese mice through up-regulation of the PPARγ/PGC-1α/UCP1 pathway

作　　者：蒋皓冉 唐晓飞 吴界霖 王姣玲 黄诚宇 祝曙光[2] 臧林泉 Jiang Haoran;Tang Xiaofei;Wu Jielin;Wang Jiaoling;Huang Chengyu;Zhu Shuguang;Zang Linquan(Pharmacology Laboratory,School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006;Dept of Cardiothoracic Surgery,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080)

机构地区：[1]广东药科大学药学院药理实验室,广州510006 [2]广东药科大学附属第一医院胸心外科,广州510080

出　　处：《安徽医科大学学报》2024年第9期1591-1598,共8页Acta Universitatis Medicinalis Anhui

基　　金：广东省自然科学基金(编号:2017A030313856)。

摘　　要：目的探究β-石竹烯(BCP)对肥胖小鼠白色脂肪棕色化的作用及其机制。方法雄性昆明小鼠高脂饮食辅以丙硫氧嘧啶生理盐水溶液[14.4 mg/(kg·d)]腹腔注射建立肥胖小鼠模型。肥胖模型小鼠随机分为模型组(Model组)和BCP给药组(BCP-50组),正常饮食小鼠设为对照组(Control组),每组8只。BCP给药组按50 mg/kg早晚灌胃给药各一次,其余组用吐温80水溶液灌胃,持续4周。4周给药结束后进行口服糖耐量实验,实验结束禁食过夜后处死小鼠,快速收集血液样本和脂肪组织用于后续实验检测。试剂盒检测血清学相关指标;苏木精-伊红染色观察脂肪组织形态;免疫组化染色观察脂肪组织解偶联蛋白1(UCP1)表达;Western blot检测附睾白色脂肪(eWAT)中过氧化物酶体增殖物激活受体γ共激活剂1-α(PGC-1α)、过氧化物酶体增殖物激活受体γ(PPARγ)、UCP1和大麻素受体2(CNR2)蛋白的表达。结果与Model组相比,BCP-50组肥胖小鼠的体质量显著减轻(P<0.05),摄食量减少(P<0.01),胰岛素抵抗得到改善(P<0.0001),肥胖小鼠血清中低密度脂蛋白胆固醇(LDL-C)和非酯化脂肪酸(NEFA)含量降低(P<0.0001和P<0.01),总胆固醇(TC)、三酰甘油(TG)和高密度脂蛋白胆固醇(HDL-C)含量无明显变化。此外,BCP-50组肥胖小鼠的脂肪系数和eWAT比重降低(P<0.05);eWAT和BAT中脂肪细胞减小,UCP1蛋白表达升高(P<0.01和P<0.05);除了UCP1外,BCP-50组肥胖小鼠eWAT中PGC1α、PPARγ和CNR2蛋白的表达水平也明显升高(P<0.01,P<0.05和P<0.001)。结论BCP通过上调PPARγ/PGC-1α/UCP1通路表达促进白色脂肪棕色化,从而改善肥胖。Objective To investigate the effects ofβ-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kunming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administration group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rapidly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptorγcoactivator1-α(PGC1α),peroxisome proliferator-activated receptorγ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adipose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05),food intake was decreased(P<0.01),insulin resistance was improved(P<0.0001),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NEFA)in the obese mice was significantly reduced(P<0.0001 and P<0.01).Total cholesterol(TC),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficie

关 键 词：β-石竹烯 白色脂肪棕色化 白色脂肪组织 附睾白色脂肪组织 过氧化物酶体增殖物激活受体Γ 过氧化物酶体增殖物激活受体γ共激活剂1-α 解偶联蛋白1 

分 类 号：R966[医药卫生—药理学] R[医药卫生—药学]