生存素下调瘦素水平并改善肥胖小鼠的瘦素敏感性  

Survivin reduces leptin expression level and improves leptin sensitivity in obese mice

作　　者：米日阿依·阿里木江 陈树青 李文菲 孙京京 陆旭红 马晓静[2] 杨颖[2] Miriayi Alimujiang;Chen Shuqing;Li Wenfei;Sun Jingjing;Lu Xuhong;Ma Xiaojing;Yang Ying(Department of Endocrinology and Metabolism,Shanghai Geriatric Medical Center,Shanghai 201100,China;Department of Endocrinology and Metabolism,Shanghai Six People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Diabetes Institute,Shanghai 200233,China)

机构地区：[1]上海市老年医学中心内分泌代谢科,上海201100 [2]上海交通大学医学院附属第六人民医院内分泌代谢科,上海市糖尿病研究所,上海200233

出　　处：《中华内分泌代谢杂志》2024年第9期763-770,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(82270906);国家自然科学基金青年科学基金项目(82300977)。

摘　　要：目的探讨生存素对瘦素转录调控及其敏感性的影响。方法用慢病毒构建过表达生存素的脂肪细胞模型,以RNA测序(RNA-seq)探讨生存素对脂肪细胞分泌蛋白表达调控的影响;通过腺相关病毒(adeno-associated virus,AAV)定点注射的方法在小鼠腹股沟脂肪组织(inguinal adipose tissue,iWAT)中实现过表达生存素,用实时荧光定量PCR(RT-qPCR)法检测瘦素、脂联素等转录水平,用酶联免疫吸附测定(ELISA)法检测细胞上清、小鼠血清中瘦素、脂联素分泌水平。用Western印迹法检测下丘脑信号转导及转录激活蛋白3(STAT3)磷酸化水平,分析生存素对中枢瘦素敏感性的影响。结果3T3-L1脂肪细胞及原代脂肪细胞中,过表达生存素在未影响脂肪细胞分化时,均可显著下调瘦素转录水平(P<0.01)。过表达生存素在未影响细胞上清中脂联素水平的同时,使瘦素水平显著下降(P<0.001)。同样,由注射AAV实现的小鼠iWAT中过表达生存素不仅可下调局部脂肪组织中瘦素转录水平,还可导致小鼠血清中瘦素分泌水平的下降(P<0.05)。在短期高脂饲料喂养小鼠中,iWAT过表达生存素小鼠下丘脑STAT3磷酸化水平增加,提示瘦素中枢敏感性改善。结论脂肪中过表达生存素可下调瘦素转录及分泌水平,改善高脂饲料喂养肥胖小鼠瘦素敏感性。Objective To investigate the role of survivin in the regulation of leptin expression and its sensitivity.Methods Survivin was overexpressed in adipocytes via lentivirus,and the RNA-sequencing(RNA-seq)was used to explore the effect of survivin on the regulation of adipocyte secretory proteins.Survivin was overexpressed in the inguinal adipose tissue(iWAT)of mice by targeted injection of adeno-associated virus(AAV).The transcription levels of leptin and adiponectin were detected by realtime quantitative PCR(RT-qPCR),and the secretion levels of leptin and adiponectin in cellular supernatants and mice serum were detected by enzyme-linked immunosorbent assay(ELISA).The protein level of phosphorylated signal transducer and activator of transcription 3(STAT3)in hypothalamus was detected by Western blotting to investigate the effect of survivin on central leptin sensitivity.Results Survivin overexpression in both 3T3-L1 and primary white adipocyte significantly down-regulated the leptin transcriptional expression without affecting the adipocyte differentiation(P<0.01).Overexpression of survivin significantly decreased leptin level without affecting the adiponectin levels in the cellular supernatant(P<0.001).Overexpression of survivin in iWAT via AAV injection,not only specifically down-regulated leptin transcriptional level in a dose dependent manner in local adipose tissue,but also led to a decrease in serum leptin level(P<0.05).In mice fed short-term high-fat diet,STAT3 phosphorylation level in hypothalamus significantly increased,suggesting improved central leptin sensitivity.Conclusion Survivin could downregulate leptin expression and improve leptin sensitivity in high-fat diet induced obese mice.

关 键 词：生存素 瘦素 瘦素敏感性 肥胖 

分 类 号：R589.2[医药卫生—内分泌]