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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(10～1000nmol/L每1×106cells)可诱导脂肪细胞脂解,因此我们预计VPAC1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(每天50nmol/kg体重)VPAC1激动剂比低剂量(每天5nmol/kg体重)有更显著的抗肥胖作用,提示VPAC1激动剂的抗肥胖作用具有剂量依赖性。以上结果表明,VPAC1激动剂不仅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。
VPAC1 is a common receptor for pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). VPAC1 mediates the biological functions of PACAP and VIP in suppressing appetite and anti-inflammatory. Our in vitro experiments showed that VPAC1 is highly expressed in differentiated 3T3-L1 adipocytes and that VPAC1 agonist (10-1000 nmol / L per 1 × 106 cells) induces lipolysis of adipocytes, and therefore we expect that VPAC1 agonists have anti- The role of obesity and obesity syndrome. In order to study the effects of VAPC1 agonist [Lys15, Arg16, Leu27] -VIP (1-7) GRF (8-27) on nutritional obesity and obesity syndrome, two groups of in vivo experiments were designed in this study: (1) NIH male mice were fed with high-fat diet for 4 weeks and intraperitoneally injected with VPAC1 agonist; saline was used as control; (2) NIH male mice were fed with high-fat diet for 5 weeks. After establishing obesity model, VPAC1 agonist was intraperitoneally injected for 4 weeks , The same injection of saline as a control. Collecting food intake, body weight, body fat, blood glucose and blood lipids and other indicators. The results showed that VPAC1 agonist significantly inhibited food intake, inhibited body weight induced by high-fat diet and body fat (epididymis and back) weight gain, and effectively improve the high-fat diet-induced hyperglycemia and hyperlipidemia and improve the body’s sugar tolerance. High doses (50 nmol / kg body weight per day) of VPAC1 agonists have a more pronounced anti-obesity effect than low doses (5 nmol / kg body weight per day), suggesting that the anti-obesity effects of VPAC1 agonists are dose-dependent. The above results show that VPAC1 agonist can not only inhibit the development of high fat-induced obesity, but also can effectively improve obesity-related diseases; its mechanism of anti-obesity is complex and integrated, which deserves further study.