紫檀芪和跑台运动诱导大鼠白色脂肪棕色化的作用

Pterostilbene and treadmill exercise induce white adipose browning in rats

目的探讨紫檀芪(pterostilbene,PST)干预和跑台运动对大鼠白色脂肪棕色化的影响及其相关分子机制。方法24只8周龄雄性SD大鼠采用随机数字表法分为4组:安静对照组(C)、PST(50 mg/kg)干预组(PST)、跑台运动组(EX)、跑台运动+PST干预组(EX+PST),干预4周。检测大鼠进食量、体质量和腹股沟白色脂肪(inguinal white adipose tissue,iWAT)质量,HE染色观察iWAT的形态学特征,实时定量PCR和Western blot检测iWAT中白色脂肪棕色化的一些标志基因和调控信号分子的表达。结果PST组、EX组、EX+PST组与对照组比较,进食量无明显变化,但体质量增加、iWAT指数明显降低(P<0.05);HE染色显示:各干预组较对照组iWAT脂肪细胞变小、变圆并伴有多室细胞出现,呈棕色化特征;同时,白色脂肪棕色化的标志基因和调控信号分子包括解偶联蛋白1(uncoupling protein 1,UCP1)、诱导细胞死亡DNA片断化因子α样效应因子A(cell death-inducing DNA fragmentation factor alpha-like effector A,CIDEA)、跨膜蛋白26(transmembrane protein 26,TMEM26)、簇分化抗原137(cluster of differentiation 137,CD137)、肉碱棕榈酰转移酶1A(carnitine palmitoyltransferase 1A,CPT1A)、细胞色素C(Cytochrome c,Cyto C)、沉默信息调节因子1(silent information regulator 1,Sirt1)、过氧化物酶体增殖活化受体γ共激活因子1α(peroxisome proliferator activator receptor gamma coactivator 1 alpha,PGC-1α)、R结构域蛋白16(PR domain-containing 16,PRDM16)等mRNA表达显著增加(P<0.05),磷酸化腺苷酸活化蛋白激酶(phosphorylated adenosine monophosphate activated protein kinase,p-AMPK)、UCP1、PRDM16蛋白水平明显升高(P<0.05)。且上述变化在EX+PST组中较PST组或EX组更为显著(P<0.05)。结论紫檀芪和跑台运动单独或联合干预均可诱导大鼠iWAT发生棕色化并降低脂肪蓄积和体质量增加,其机制可能与AMPK信号转导途径激活有关,且二者联合干预效应优于单一因素干预。

ObjectiveTo investigate the effects of pterostilbene(PST)intervention and treadmill exercise on browning of white adipose in rats and explore the molecular mechanisms.MethodsTwenty-four 8-week-old male SD rats were randomly divided into 4 groups:sedentary control group(C),50 mg/kg PST treatment group,treadmill exercise(EX)group,and treadmill exercise with PST treatment(EX+PST)group.After corresponding treatments for 4 consecutive weeks,the rats were evaluated for changes in food intake,body weight and inguinal white adipose tissue(iWAT)mass.The morphological features of the iWAT were analyzed with HE staining.The mRNA and protein levels of the marker genes and the regulatory molecules for white fat browning in the iWAT were determined using real-time quantitative PCR and Western blotting,respectively.ResultsThe body weight gain and iWAT index in the 3 treatment groups were all significantly lower than those of the control group(P<0.05),while food intake did not differ significantly among the 4 groups.Compared with those in the control group,the adipocytes within the iWAT in the 3 treatment groups showed a smaller size and a more spherical morphology accompanied by the presence of cellular compartmentation,which were all characteristics of brown adipocytes.The mRNA and protein levels of the marker genes and regulatory molecules for white adipose browning,including uncoupling protein 1(UCP1),cell death-inducing DNA fragmentation factor alpha-like effector A(CIDEA),cluster of differentiation 137(CD137),transmembrane protein 26(TMEM26),carnitine palmitoyltransferase 1A(CPT1A),cytochrome c(Cyto c),silent information regulator 1(Sirt1),peroxisome proliferator activator receptor gamma coactivator 1 alpha(PGC-1α),PR domain-containing 16(PRDM16)and phosphorylated adenosine monophosphate activated protein kinase(p-AMPK)were all significantly increased in the iWAT in the 3 treatment groups(P<0.05).These changes were more obvious in EX+PST group than in EX group and PST group(P<0.05).ConclusionPST intervention and treadmill exercise,either alone or in combination,can induce the browning of iWAT and reduce fat accumulation and body weight gain in rats through a mechanism possibly involving the activation of AMPK signal transduction pathway.PST combined with treadmill exercise produces more pronounced effects than either PST or treadmill exercise alone.