肥胖大鼠瘦素信号传导通路的变化

目的筛选与人类代谢障碍性肥胖症发病病因学相似的肥胖大鼠模型,并对肥胖个体Leptin信号传导通路的改变情况进行初步研究。方法离乳雄性Wistar大鼠以高脂饲料喂养6周后,取体重增加值大的前1/4部分作为肥胖倾向组大鼠。对肥胖倾向组大鼠,继续进行高脂饲料喂养,并观察其体重、血清Leptin的变化趋势;试验49周后,大鼠处死,对内脏脂肪含量、附睾脂肪细胞大小以及下丘脑LRb（Leptin受体b亚型）表达水平及Stat3磷酸化水平（Tyr705磷酸化）进行测定。结果正常对照组大鼠和肥胖倾向组大鼠在不同饲料喂养的第17周开始体重相对增加值出现组间显著性差异;除第16周肥胖倾向组大鼠的血清Leptin浓度高于正常对照组,但不存在显著性差异之外,其它采血时间点,肥胖倾向组的血清Leptin浓度均显著高于正常对照组;动物处死后,肥胖倾向组大鼠的内脏脂肪含量和附睾脂肪细胞大小均显著大于正常对照组;两组大鼠在下丘脑LRb表达水平和细胞浆内Stat3磷酸化水平方面不存在显著性差异。结论本研究得到了与营养性肥胖人群临床表现相似的肥胖大鼠;同时发现,肥胖大鼠在长期高浓度Leptin刺激后,可能引起了中枢性Leptin抵抗,致使Leptin对体重调节的正常生理作用受到抑制,脂代谢异常的程度进一步加深,最终表现为脂肪细胞体积增大、内脏脂肪含量升高和体重增加。

Changes of Leptin Signal Pathway in Rat Obesity Progression

Objective To screen obesity rat model of metabolic disturbance,and to determine whether Leptin signal transduction pathway in obesity rats are changed or not.Method Male Wistar weaning rats were divided randomly into control group and high-fat fed group.Rats of high-fat fed group were fed high-fat diet for 6 weeks,and then,screened them based on body weight gain（upper quarter for obesity-prone rats）.During the dietary period,body weight and serum Leptin level of obesity-prone group rats and control group rats were determined on schedule;Rats were decapitated 12 months later,content of body lipid,size of epididymis fat cell and protein expression level of LRb,Stat3 and p-Stat3 in hypothalamus were determined as well.Result Both body weight and relative added body weight had got significant differences between control group and obesity-susceptible group after the 17th week feeding;serum Leptin level had significant differences between control group and obesity-susceptible group except for the 16th week;Percent of body lipidsand the size of epididymis fat cell had got significant differences between control group and obesity-susceptible group after the special diet feeding for 49 weeks;LRb protein expression level and Stat3 phosphorylation level in hypothalamus had no differences between obesity-susceptible group and control group.Conclusion Our study got the first generation of obesity rat model which had the similarly pathogenesis and clinical symptoms successfully.The down-regulation of LRb must be a key factor charged for the disregulation of lipid metabolism.