GHS-R1a对高脂饮食小鼠糖代谢及腹部脂肪影响

EFFECT OF GROWTH HORMONE SECRETAGOGUE RECEPTOR 1A ON GLUCOSE METABOLISM AND ABDOMINAL FAT IN MICE FED WITH HIGH-FAT DIET

目的探讨生长激素促分泌素受体(GHS-R)1a对高脂饮食小鼠体质量、腹部脂肪组织及糖代谢的影响。方法选取6周龄野生型(WT)雌性C57BL/6小鼠10只,随机分为普通饮食组(WTRD组,n=5)和高脂饮食组(WT HFD组,n=5);选取6周龄GHS-R1a基因敲除(KO)雌性C57BL/6小鼠10只,随机分为普通饮食组(KORD组,n=6)和高脂饮食组(KO HFD组,n=4)。于6~15周龄每周测量体质量;于16周龄时行腹腔葡萄糖耐量试验(IPGTT),分别于注射后0、15、30、60、120min行尾静脉取血测定血糖;于17周龄时将小鼠安乐死后取出肝脏和腹内白色脂肪组织并称质量,制备石蜡切片观察腹内脂肪病理变化。结果对各组小鼠15周龄较6周龄体质量变化量进行比较,WTHFD组明显高于WTRD组(F=6.99,P<0.05),而KO HFD组与KORD组差异无显著性(P>0.05)。17周龄时,WT HFD组小鼠腹内脂肪质量、腹内脂肪比例均显著大于KO HFD组(F=4.79、6.39,P<0.05),而WTRD组与KORD组比较差异均无显著性(P>0.05)。组织学观察显示,KO HFD组小鼠脂肪细胞面积较WT HFD组小(F=12.30,P<0.01)。WT HFD组小鼠空腹血糖水平显著高于KO HFD组(P<0.01),空腹胰岛素水平也显著高于KO HFD组(F=26.88,P<0.01)。对各组小鼠IPGTT曲线下面积(AUC)进行比较,WT HFD组明显高于KO HFD组(F=6.40,P<0.05)。结论小鼠GHS-R1a敲除可以抵抗高脂饮食诱导的肥胖、腹部脂肪堆积,改善胰岛素敏感性和糖耐量异常。

Objective To investigate the effect of growth hormone secretagogue receptor 1a(GHS-R1a)on the body weight,abdominal adipose tissue,and glucose metabolism of mice fed high-fat diet.Methods Ten wild-type(WT)female C57BL/6 mice,aged 6 weeks,were selected and randomly divided into regular diet group(WT RD with 5 mice)and high-fat diet group(WT HFD with 5 mice);10 female C57BL/6 mice withGHS-R1a gene knockout(KO),aged 6 weeks,were randomly divided into regular diet group(KO RD group with 6 mice)and high-fat diet group(KO HFD group with 4 mice).Body weight was measured on a weekly basis from the age of 6-15 weeks;the intraperitoneal glucose tolerance test(IPGTT)was performed at the age of 16 weeks,and blood samples were collected via the caudal vein at 0,15,30,60,and 120 min after injection to measure blood glucose;after the mice were euthanized at the age of 17 weeks,the liver and the white abdominal adipose tissue were collec-ted and weighed,and paraffin sections were used to observe the pathological changes of abdominal adipose tissue.Results The change in body weight from the age of 6 weeks to 15 weeks was compared between groups,and the WT HFD group had a significantly higher body weight than the WT RD group(F=6.99,P<0.05),while there was no significant difference between the KO HFD group and the KO RD group(P>0.05).At the age of 17 weeks,the WT HFD group had significantly higher weight and proportion of intra-abdominal fat than the KO HFD group(F=4.79,6.39;P<0.05),but there was no significant difference between the WT RD group and the KO RD group(P>0.05).Histological analysis showed that the KO HFD group had a significantly smaller adipocyte area than the WT HFD group(F=12.30,P<0.01).Compared with the KO HFD group,the WT HFD group had significantly higher levels of fasting blood glucose(P<0.01)and fasting insulin(F=26.88,P<0.01).The area under the IPGTT curve was compared between groups,and the WT HFD group had a significantly larger area than the KO HFD group(F=6.40,P<0.05).Conclusion GHS-R1a knockout in mice can resist obesity and abdominal fat accumulation induced by high-fat diet and improve insulin sensitivity and abnormal glucose tolerance.