妊娠期和哺乳期母鼠果糖暴露调控仔鼠食欲的机制中JAK2/STAT3信号通路研究

Child obesity is closely associated with increased appetite. The Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) is an important pathway on hypothalamic appetite regulation. Recent studies have found that maternal high fructose during pregnancy and lactation may damage hypothalamic appetite regulation in offspring and that is closely related to obesity of generations. However, it is still largely unknown by which mechanism maternal high fructose during pregnancy and lactation damage hypothalamic appetite regulation in offspring. Leptin is an important factor on the appetite regulation of central nervous system. Leptin may activate JAK2/STAT3 signal transduction pathway to inhibit neuropeptide Y (NPY), promote releasing of α-melanocyte-stimulating hormone (α-MSH) and activate suppressor of cytokine signaling 3 (SOCS3), thereby regulating food intake and energy metabolism. Through gestation and lactation, maternal exposed fructose model was established in SD rats using drinking water with different concentrations of fructose. We will detect the levels of leptin, NPY and α-MSH in serum at different developmental stages of pups and the levels of JAK2/STAT3/SOCS3, NPY and proopiomelanocortin in the hypothalamus of pups to reveal the time-dose-response relationship of offspring appetite following maternal fructose exposure and the key target for the central regulation of appetite during pregnancy and lactation.

儿童肥胖发生与食欲增强密切相关。Janus 激酶2（JAK2）/转录激活因子3（STAT3）信号途径是下丘脑食欲调节的重要转导通路。最近研究发现，妊娠期和哺乳期母体高果糖暴露可能损伤子代下丘脑对食欲的调控作用，且与后代肥胖发生有关，但机制还未阐明。瘦素是调控中枢神经系统食欲的重要因子。瘦素可通过激活JAK2/STAT3信号通路抑制神经肽Y（NPY）递质、促进α-促黑素细胞激素（α-MSH）递质释放，同时激活细胞因子信号转导抑制剂3（SOCS3），进而调节食物摄入量。因此，本研究采用妊娠期和哺乳期大鼠通过饮水途径暴露不同浓度果糖，研究不同发育期仔鼠血清中瘦素、NPY及α-MSH和仔鼠下丘脑中JAK2/STAT3/SOCS3、NPY及前阿黑皮素的变化，揭示妊娠期和哺乳期果糖母体暴露对仔鼠食欲影响的时间剂量效应关系及影响中枢食欲调控的关键靶点。