Abstract: Objective To explore whether high fat diet-induced obesity and leptin resistance are attenuated by silencing suppressor of cytokine signaling 3(SOCS3) by means of RNA interference(RNAi) in young rats. Methods A total of 32 five-week-old Sprague-Dawley (SD) rats were divided into 4 groups randomly.The lentiviral vector(LV)-SOCS3-shRNA(RNAi) or LV-control-shRNA(Con) were stereotaxically injected bilaterally into the lateral ventricle of rats which then fed with hight-fat diet(HFD) or chow diet (CD) for 28 days, designated as RNAi+CD group, Con+CD group, RNAi+HFD group and Con+HFD group.Food intake and body weight were measured every 2 days and 7 days respectively.Up to 28 days after treatment, blood was harvested from the four group rats.Then levels of leptin, plasma glucose (PG), total cholesterol (TC) and triglycerides (TG) were detected by radioimmunity assay or automatic biochemistry analyzer respectively. Results Cumulative food intake and body weight of rats treated with RNAi+HFD exhibited decrease compared with those treated with Con+HFD after injection of 14 days and 21 days respectively (P＜0.05), but showed increase compared with those treated with Con+CD after injection of 22 days and 28 days respectively (P＜0.05).Level of leptin in rats treated with RNAi+HFD (0.86±0.12) ng/mL was significantly lower than those treated with Con+HFD (0.97±0.13) ng/mL and higher than those treated with Con+CD(0.75±0.10)ng/mL (P＜0.05). Conclusions Knockdown of SOCS3 by RNAi partly relieves high fat diet-induced obesity and leptin resistance in young rats.

Key words: obesity, young rats, RNA interference, suppressor of cytokine signaling 3

摘要： 目的 观察RNA干扰(RNA interference, RNAi)沉默细胞因子信号转导抑制因子3(suppressor of cytokine signaling3, SOCS3)能否改善高脂喂养幼年大鼠的肥胖和瘦素抵抗。方法 32只5周龄健康雄性SD大鼠, 随机分为4组干扰+普食组, 对照+普食组, 干扰+高脂组, 对照+高脂组, 每组各8只。侧脑室注射慢病毒载体SOCS3干扰液或慢病毒载体对照液, 然后给予高脂或普通饲料喂养28 d, 期间测摄食量和体重。处死后取血, 放射免疫法测瘦素(leptin)含量, 全自动生化分析仪测血糖(plasma glucose, PG)、总胆固醇(total cholesterol, TC)、甘油三脂(triglycerides, TG)水平。结果 干扰+高脂组大鼠的摄食量和体重分别于注射后第14天和第21天起低于对照+高脂组(P＜0.05);于注射后第22天起和第28天高于对照+普食组(P＜0.05)。干扰+高脂组大鼠瘦素水平(0.86±0.12)ng/mL低于对照+高脂组(0.97±0.13)ng/mL, 高于对照+普食组(0.75±0.10)ng/mL(P＜0.05)。结论 SOCS3基因沉默可改善幼年大鼠高脂喂养诱导的肥胖和瘦素抵抗。

关键词: 肥胖, 幼年大鼠, RNA干扰, 细胞因子信号转导抑制因子3