脂肪组织RAP1B敲除缓解寒冷条件下肥胖小鼠的脂肪积累  

Knockout of RAP1B in Adipose Tissue Decreases Fat Accumulation in Obese Mice under Cold Conditions

作　　者：傅寅旭 朱辉 王鑫波 胡萍乙 方毓 周怀彬 吕建新 FU Yinxu;ZHU Hui;WANG Xinbo;HU Pingyi;FANG Yu;ZHOU Huaibin;LÜJianxin(School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China;School of Laboratory Medicine and Bioengineering,Hangzhou Medical College,Hangzhou 310053,China)

机构地区：[1]温州医科大学检验医学院、生命科学学院,温州325035 [2]杭州医学院检验医学院、生物工程学院,杭州310053

出　　处：《中国细胞生物学学报》2024年第11期1881-1893,共13页Chinese Journal of Cell Biology

基　　金：浙江省自然科学基金(批准号:LY24H200002);温州市基础性科研项目(批准号:Y2023090)资助的课题。

摘　　要：该研究旨在探讨RAP1B在脂肪组织细胞代谢功能调节中的作用机制。围绕高脂饮食喂养和冷刺激处理的脂肪组织特异性Rap1b敲除小鼠,结合RAP1B敲低的3T3-L1细胞模型,系统分析RAP1B对白色脂肪组织线粒体功能的影响。通过对比脂肪组织特异性敲除Rap1b小鼠与对照组小鼠在脂肪组织中的体质量、脂肪组织含量、脂质代谢相关指标和体温调节能力,评估RAP1B在脂肪组织代谢中的作用,结果表明,RAP1B缺失的小鼠在HFD喂养下夜间体温显著升高,脂肪含量下降。3T3-L1细胞实验结果显示,RAP1B敲低不影响脂肪细胞分化和脂质积累,但显著提高了线粒体的呼吸功能和ATP产量。进一步研究发现,RAP1B缺失显著提高了小鼠脂肪组织和3T3-L1细胞的线粒体复合体含量,脂肪组织蛋白组学结果显示氧化磷酸化和产热途径富集。这些结果表明,RAP1B缺失后可能通过增强线粒体功能改善脂肪组织的代谢能力,进而影响体温调节和脂质储存。该研究揭示了RAP1B在脂肪组织线粒体功能调节中的关键作用,并提出RAP1B缺失后可能通过增强线粒体功能和改变脂质代谢状态影响肥胖的发展。This study aims to explore the role of RAP1B in regulating metabolic functions in adipose tissue and its implications in obesity.Using adipose tissue-specific Rap1b knockout mice subjected to HFD(highfat diet)feeding and cold exposure,along with RAP1B knockdown 3T3-L1 cell models,the impact of RAP1B on mitochondrial function was systematically analyzed in white adipose tissue.By comparing Rap1b knockout mice with control mice,body weight,fat content,lipid metabolism indicators,and thermoregulation ability were assessed in adipose tissue.Results revealed that RAP1B-deficient mice exhibited significantly elevated nocturnal body temperature and reduced fat content under HFD conditions.In 3T3-L1 cells,RAP1B knockdown did not affect adipocyte differentiation or lipid accumulation but significantly enhanced mitochondrial respiratory function and ATP production.Further investigations showed that RAP1B deficiency markedly increased mitochondrial complex content in both mouse adipose tissue and 3T3-L1 cells.Proteomic analysis of adipose tissue indicated enrichment in oxidative phosphorylation and thermogenic pathways.These findings suggest that RAP1B may improve adipose tissue metabolic capacity by enhancing mitochondrial function,thereby influencing thermoregulation and lipid storage.This study highlights the critical role of RAP1B in regulating mitochondrial function in adipose tissue and proposes that RAP1B may impact the development of obesity by modulating mitochondrial activity and lipid metabolism.

关 键 词：RAP1B 肥胖 线粒体功能 脂肪组织 能量代谢 代谢性疾病 

分 类 号：R589.2[医药卫生—内分泌]