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作 者:马筱璇 高菲 逯素梅[1] 玄晓蕾 张永娇 石晓红[1] MA Xiaoxuan;GAO Fei;LU Sumei;XUAN Xiaolei;ZHANG Yongjiao;SHI Xiaohong(Department of Clinical Laboratory Medicine,the First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,Key Laboratory of Clinical Laboratory Diagnostics for Medicine and Health of Shandong Province,Jinan 250014,China;School of Medical Laboratory,Shandong Second Medical University,Weifang 261053,China)
机构地区:[1]山东第一医科大学第一附属医院(山东省千佛山医院)检验科,山东省医药卫生临床检验诊断重点实验室,山东济南250014 [2]山东第二医科大学医学检验学院,山东潍坊261053
出 处:《山东第一医科大学(山东省医学科学院)学报》2025年第2期72-82,共11页Journal of Shandong First Medical University & Shandong Academy of Medical Sciences
基 金:山东省自然科学基金(ZR2023MH031,ZR2023QH232);山东第一医科大学青年科学基金培育支持计划(202201-083)。
摘 要:目的 寻找肥胖能量平衡控制过程中,调控蛋白质翻译启动的关键因子。方法 通过高通量RNA测序分析肥胖者和健康对照者大网膜脂肪组织中差异表达的mRNA。通过基因本体(gene ontology, GO)富集、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路分析将差异表达的mRNA进行功能富集,围绕真核生物翻译起始家族(eukaryotic translation initiation family,eIFs)进一步分析,并通过GEPIA/GEO数据库验证、免疫印迹实验及qPCR验证eIFs在ob/ob小鼠、db/db小鼠、原代脂肪细胞和C3H10T1/2细胞分化模型中的表达情况。结果 肥胖症患者大网膜脂肪组织中,翻译起始因子3e(eukaryotic initiation factor 3e, eIF3e)表达量下降显著。eIF3e与肥胖相关代谢表型和脂肪生成相关基因呈负相关。在培养的原代脂肪细胞和C3H10T1/2细胞诱导分化过程中,发现eIF3e在脂肪生成过程中发挥负调控作用。在β3肾上腺素能刺激下,在适应性产热小鼠模型和C3H10T1/2细胞中检测到伴随能量的消耗eIF3e正向升高。结论 eIF3e在脂肪生成过程中表达下调,且脂肪分解过程中表达上调,提示eIF3e可能是肥胖能量平衡控制过程中,调控蛋白质翻译启动的关键因子。Objective:Find the key factors regulating the initiation of protein translation in the process of controlling energy balance in obesity.Methods:This study analyzes the differentially expressed mRNAs in omental adipose tissue of obese individuals and healthy controls by high-throughput RNA sequencing,and finds abnormal translation initiation levels.The differentially expressed mRNAs are functionally enriched by GO enrichment and KEGG pathway analysis,and further analyzed around the eukaryotic translation initiation family(eukaryotic translation initiation family,eIFs),and the expression of eIFs in ob/ob mice,db/db mice,primary adipocytes and C3H10T1/2 cell differentiation models is verified by GEPIA/GEO database verification,Western blotting experiments and qPCR.Results:In the omental adipose tissue of obese patients,the expression of translation initiation factor 3e(eIF3e)decreases significantly.The GEPIA/GEO database confirms the negative correlation between eIF3e and obesity-related metabolic phenotypes and adipogenesis-related genes.During the induction and differentiation of primary adipocytes and C3H10T1/2 cells in culture,the negative regulatory role of eIF3e in adipogenesis has been discovered.Underβ3 adrenergic stimulation,the positive increase of eIF3e accompanied by energy expenditure has been detected in the adaptive thermogenesis mouse model and C3H10T1/2 cells.Conclusion:eIF3e is downregulated during adipogenesis and upregulated during lipolysis,suggesting that eIF3e may be a key factor in regulating the initiation of protein translation during the control of energy balance in obesity.
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