京尼平对小鼠棕色和白色脂肪组织UCP1表达的影响
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摘要
目的:棕色脂肪组织活化和白色脂肪组织棕化是改善减肥的良好策略。本研究利用冷刺激作为阳性对照,观察京尼平对小鼠脂肪组织活化与棕化的作用。方法:8周龄雄性C57BL/6J小鼠30只,随机分为正常对照组、京尼平组、冷刺激组,每组10只。京尼平组小鼠腹腔注射给予京尼平处理(15 mg/(kg·d),连续9 d),对照组用生理盐水处理,冷刺激组小鼠在室温(22℃±2℃)下处理4 d后,置于4℃环境中进行冷刺激处理5 d(24 h/d)。检测各组小鼠每天摄食量、体重和体温变化,取肩胛下区、腹股沟区及附睾周围部分脂肪组织观察形态学的变化,测定棕色脂肪组织、皮下白色脂肪组织以及内脏白色脂肪组织解偶联蛋白1(UCP1)的表达。结果:与正常对照组相比,京尼平组小鼠白色脂肪湿重下降16%,冷刺激组下降28%,均有明显差异(P<0.05);京尼平组和冷刺激组白色脂肪组织颜色变深,HE染色显示脂肪细胞内的脂滴变小,数量增加;京尼平组小鼠的皮下、内脏白色脂肪组织和棕色3种脂肪组织中的UCP1表达量均明显增加(P<0.05)。结论:京尼平通过上调UCP1的表达促进棕色脂肪组织活化和白色脂肪组织棕化,此效应是京尼平降脂减轻体重的作用机制之一。
Objective: To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.Methods: The male C57 BL/6 J mice were divided into three groups: normal control group,genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days,normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region,inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1( UCP1) was determined by real-time PCR and Western blot respectively.Results: The wet weight of white fat in genipin-treated mice was decreased by 16%,and 28% in that of cold-stimulus mice,compared with the normal control group( P<0.05).After treatments of genipin and cold-stimulus,the color of white adipose tissues was darker,and the size of lipid droplets in adipocytes was smaller,whereas the number was increased.Compared with the normal control group,UCP1 expression was increased obviously in fat tissues,including the subcutaneous and visceral white adipose tissues,and brown adipose tissue after treated with genipin and cold-stimulus( P<0.05).Conclusion: Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression,which could contribute to the loss of body weight against obesity.
Objective: To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.Methods: The male C57 BL/6 J mice were divided into three groups: normal control group,genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days,normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region,inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1( UCP1) was determined by real-time PCR and Western blot respectively.Results: The wet weight of white fat in genipin-treated mice was decreased by 16%,and 28% in that of cold-stimulus mice,compared with the normal control group( P<0.05).After treatments of genipin and cold-stimulus,the color of white adipose tissues was darker,and the size of lipid droplets in adipocytes was smaller,whereas the number was increased.Compared with the normal control group,UCP1 expression was increased obviously in fat tissues,including the subcutaneous and visceral white adipose tissues,and brown adipose tissue after treated with genipin and cold-stimulus( P<0.05).Conclusion: Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression,which could contribute to the loss of body weight against obesity.
引文
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[19]Elias I,Franckhauser S,FerréT,et al.Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance[J].Diabetes,2012,61(7):1801-1813.
[20]Sun K,Wernstedt Asterholm I,Kusminski CM,et al.Dichotomous effects of VEGF-A on adipose tissue dysfunction[J].Proc Natl Acad Sci USA,2012,109(15):5874-5879.
[21]Seale P,Kajimura S,Yang W,et al.Transcriptional control of brown fat determination by PRDM16[J].Cell Metab,2007,6(1):38-54.
[2]Cinti S.The adipose organ at a glance[J].Dis Model Mech,2012,5(5):588-594.
[3]许冬明,李显国.高脂饮食及运动对2型糖尿病大鼠脂联素、瘦素及血糖水平的影响[J].中国应用生理学杂志,2016,32(4):298-300.
[4]Calvani R,Leeuwenburgh C,Marzetti E.Brown adipose tissue and the cold war against obesity[J].Diabetes,2014,63(12):3998-4000.
[5]Kim SJ,Kim JK,Lee DU,et al.Genipin protects lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice[J].Eur J Pharmacol,2010,635(1-3):188-193.
[6]Rajanbabu V,Galam L,Fukumoto J,et al.Genipin suppresses NLRP3 inflammasome activation through uncoupling protein-2[J].Cell Immunol,2015,297(1):40-45.
[7]Guan L,Feng H,Gong D,et al.Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction[J].Exp Gerontol,2013,48(12):1387-1394.
[8]Mahgoub E,Kumaraswamy SM,Kader KH,et al.Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress,inflammation,and apoptosis[J].Biomed Pharmacother,2017,93:1083-1097.
[9]Dando I,Pacchiana R,Pozza ED,et al.UCP2 inhibition induces ROS/Akt/m TOR axis:Role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism[J].Free Radic Biol Med,2017,113:176-189.
[10]吕艺,杜桂仙.对冷适应大鼠棕色脂肪和肝脏在非寒颤产热机制中作用的评价[J].中国应用生理学杂志,1992,8(3):237-241.
[11]Langin,D Recruitment of brown fat and conversion of white into brown adipocytes:strategies to fight the metabolic complications of obesity[J]?Biochim Biophys Acta,2010,1801(3):372-376.
[12]Sharp LZ,Shinoda K,Ohno H,et al.Human BAT possesses molecular signatures that resemble beige/brite cells[J].Plos One,2012,7(11):e49452.
[13]Rosenwald M,Perdikari A,Rülicke T,et al.Bi-directional interconversion of brite and white adipocytes[J].Nat Cell Biol,2013,15(6):659-667.
[14]Bartelt A,Heeren J.Adipose tissue browning and metabolic health[J].Nat Rev Endocrinol,2014,10(1):24-36.
[15]Jia R,Luo XQ,Wang G,et al.Characterization of coldinduced remodelling reveals depot-specific differences across and within brown and white adipose tissues in mice[J].Acta Physiol,2016,217(4):311-324.
[16]Zhang Z,Zhang H,Li B,et al.Berberine activates thermogenesis in white and brown adipose tissue[J].Nat Commun,2014,5:5493.
[17]Qian SW,Tang Y,Li X,et al.BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis[J].Proc Natl Acad Sci USA,2013,110(9):E798-807.
[18]Lim S,Honek J,Xue Y,et al.Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice[J].Nat Protoc,2012,7(3):606-615.
[19]Elias I,Franckhauser S,FerréT,et al.Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance[J].Diabetes,2012,61(7):1801-1813.
[20]Sun K,Wernstedt Asterholm I,Kusminski CM,et al.Dichotomous effects of VEGF-A on adipose tissue dysfunction[J].Proc Natl Acad Sci USA,2012,109(15):5874-5879.
[21]Seale P,Kajimura S,Yang W,et al.Transcriptional control of brown fat determination by PRDM16[J].Cell Metab,2007,6(1):38-54.