CAJ | 학술논문

VPAC1是垂体腺苷酸环化酶激活多肽(pituitary adenylate cyclase-activating polypeptide,PAcAP)和血管活性肠肽(Vasoactive intestinal polypeptide,VIP)的共同受体.VPAC1介导PACAP和VIP抑制食欲和抗炎的生物学功能.本研究体外实验表明,VPAC1在分化成熟的3T3-L1脂肪细胞中表达增高,并且VPAC1激动剂(10～1000 nmol/L每1x106 cells)可诱导脂肪细胞脂解,冈此我们预计VPACl激动剂具有抗肥胖及肥胖综合征的作用.为研究VAPC1激动剂[Lys15,Arg16,Leu27]-VIP(1-7)GRF(8-27)对营养性肥胖及肥胖综合征的干预作用,本研究又设计了两组体内实验:(1)高脂喂养NIH雄性小鼠4周,同时腹腔注射VPAC1激动剂;以注射生理盐水作为对照;(2)高脂喂养NIH雄性小鼠5周,构建肥胖模型后,再腹腔注射VPAC1激动剂4周,同样以注射生理盐水作为对照.采集摄食、体重、体脂、血糖及血脂等指标.结果显示,VPAC1激动剂显著抑制摄食、抑制高脂饮食诱导的体重及体脂(附睾及背部)重量的增长,并有效改善高脂饮食诱导的高血糖及高血脂,提高机体的糖耐受.高剂量(每大50 nmol/kg体莺)VPACl激动剂比低剂量(每天5 nmol/kg体重)有更显著的抗肥胖作用,VPAC1激动剂的抗肥胖作用具有剂量依赖性.以上结果表明,VPAC1激动剂小仪能抑制高脂诱导的肥胖的发展,而且可有效改善肥胖相关疾病:其抗肥胖作用的机制是复杂整合的,值得进一步深入研究.
VPAC1시수체선감산배화매격활다태(pituitary adenylate cyclase-activating polypeptide,PAcAP)화혈관활성장태(Vasoactive intestinal polypeptide,VIP)적공동수체.VPAC1개도PACAP화VIP억제식욕화항염적생물학공능.본연구체외실험표명,VPAC1재분화성숙적3T3-L1지방세포중표체증고,병차VPAC1격동제(10～1000 nmol/L매1x106 cells)가유도지방세포지해,강차아문예계VPACl격동제구유항비반급비반종합정적작용.위연구VAPC1격동제[Lys15,Arg16,Leu27]-VIP(1-7)GRF(8-27)대영양성비반급비반종합정적간예작용,본연구우설계료량조체내실험:(1)고지위양NIH웅성소서4주,동시복강주사VPAC1격동제;이주사생리염수작위대조;(2)고지위양NIH웅성소서5주,구건비반모형후,재복강주사VPAC1격동제4주,동양이주사생리염수작위대조.채집섭식、체중、체지、혈당급혈지등지표.결과현시,VPAC1격동제현저억제섭식、억제고지음식유도적체중급체지(부고급배부)중량적증장,병유효개선고지음식유도적고혈당급고혈지,제고궤체적당내수.고제량(매대50 nmol/kg체앵)VPACl격동제비저제량(매천5 nmol/kg체중)유경현저적항비반작용,VPAC1격동제적항비반작용구유제량의뢰성.이상결과표명,VPAC1격동제소의능억제고지유도적비반적발전,이차가유효개선비반상관질병:기항비반작용적궤제시복잡정합적,치득진일보심입연구.
It was hypothesized that the VPAC1 agonist may exert anti-obesity functions because VPACI is involved in the anorexigenic effects and the anti-inflammatory function of pituitary adenylate cyclase-activating polypeptide(PACAP)/vasoactive intestinal polypeptide(VIP).Furthermore,our in vitro test showed that the expression of VPAC 1 increased significantly after the 3T3-L1 adipocytes were differentiated,and that incubation of adipocytes with VPACI agonist(10-1 000 nmol/L per 1x 106 cells)resulted in stimulation of lipolysis.To test the effect of VPAC1 agonist[Lys15,Arg16,Leu27]-VIP(1-7)GRF(8-27)on diet-induced obesity(DIO),we fuaher designed the following two in vivo experiments:(1)Mice were fed on high-fat diet(HFD)and intraperitoneally(i.P.)treated with VPAC 1 agonist simultaneously for 28 d;(2)Mice were given HFD for 35 d,and subsequently fed on the same HFD and i.p.treated with VPAC1 agonist for the next 28 d.The physiological indices,including body weight,weight of white adipose tissue,plasma glucose and b100d lipid.were collected.The results showed that treatment with VPAC1 agonist inhibited ingestion significantly and prevented the elevations in bedv weight and the weights of the white adipose tissues(epididymai and dorsal)induced by HFD.The increases in plasma glucose,cholesterol,triglycerides and LDL induced by HFD were also down-regulated in mice treated with VPAC1 agonist.VPAC I agonist treatment also improved the glucose tolerance.Therefore,VPAC1 agonist treatment inhibits the development of the obesity induced by HFD and helps to improve the morbidities associated with DIO.