母鼠肥胖通过子鼠下丘脑SOCS3-JAK/STAT通路影响采食量的研究

Obese maternal mice influence the feed intake of offsprings via SOCS3-JAK/STAT pathway in the hypothalamus

目的探讨母鼠肥胖对子鼠下丘脑细胞因子信号转导抑制因子3-Janus激酶/信号转导子和转录激活物(SOCS3-JAK/STAT)通路的影响,为预防肥胖等慢性代谢综合征的发生提供新思路。方法分别通过高脂及普通饲料喂养C57BL/6J母鼠建立肥胖母鼠(OM)组及非肥胖母鼠(NM)组,每组10只。每只母鼠所产子鼠均随机选取1只组成OM组子鼠(OM-D)及NM组子鼠(NM-D),每组10只,哺乳4周后予相同高脂饲料喂养,至第17周结束时比较两组体重、采食量及血清瘦素(Leptin)等指标;采用实时定量PCR法检测SOCS3、Leptin受体(LEPR)、刺鼠相关蛋白(AGRP)及阿黑皮素原(POMC)mRNA表达水平;采用Western blot法检测SOCS3、磷酸化的JAK2(P-JAK2)、JAK2、磷酸化的STAT3(P-STAT3)、STAT3蛋白表达水平。结果与NM-D组相比,OM-D组17周体重、采食量均显著增高,血清Leptin水平增加(均P<0.05);SOCS3、AGRP、POMC mRNA表达水平的差异均有统计学意义(均P<0.05),而LEPR mRNA表达水平的差异无统计学意义(P>0.05);SOCS3蛋白表达水平显著增高,P-JAK2/JAK2明显降低(均P<0.05);P-STAT3/STAT3也有下降趋势,但差异无统计学意义(P>0.05)。结论母鼠肥胖会导致子鼠下丘脑SOCS3 mRNA表达水平增加,从而抑制Leptin-JAK/STAT信号通路活性,导致AGRP mRNA表达水平升高,POMC mRNA表达水平下降,最终导致采食量增加,进而诱发肥胖。

Objective To investigate the effect of obese maternal mice on the SOCS3-JAK/STAT pathway of offsprings.Methods C57BL/6J female mice were fed with high fat diet to establish obese maternal model(OM group,n=10)and the non-obese maternal mice(NM group,n=10)were fed with chow diet.The offsprings from OM-D or NM-D groups(OM-D group and NM-D group,n=10 for each group)were fed with the same high fat diet from age of 4 weeks to 17 weeks.The body weight,feed intake and serum leptin level were compared between the two groups.Quantitative real-time RT-PCR and Western blot were performed to detect the relative expression of appetite related genes SOCS3,LEPR,AGRP,POMC and the activity of JAK/STAT signaling pathway in hypothalamus of offspring mice.Results Compared with NM-D group,OM-D group exhibited higher body weight and food intake(P<0.05),higher level of serum Leptin(P<0.05).There were significant differences among SOCS3,AGRP and POMC mRNA(P<0.05),but there was no significant difference among LEPR mRNA(P>0.05),SOCS3 protein expression was significantly increased,P-JAK2/JAK2 were significantly decreased(P<0.05),P-STAT3/STAT3 also showed a trend of decline,but the difference was not statistically significant(P>0.05).Conclusion The expression of AGRP mRNA is up-regulated and the expression of POMC mRNA is down-regulated,leading to the increased feed intake and inducing obesity in offspring mice of the obese maternal mice,which is associated with the inhibition of leptin-JAK/STAT signal pathway activity in the hypothalamus.