江苏大学学报(医学版)2025,Vol.35Issue(6):487-495,9.DOI:10.13312/j.issn.1671-7783.y250019
细胞外基质蛋白SVEP1对脂肪细胞脂解及产热功能的影响
Effects of extracellular matrix protein SVEP1 on lipolysis and thermogenesis in adipocytes
摘要
Abstract
Objective:To investigate the effects of extracellular matrix(ECM)protein SVEP1 on lipolysis and thermogenesis in adipocytes.Methods:The RNA-seq database of abdominal subcutaneous adipose tissue(SAT)of 236 normal and obese individuals constructed previously was used to analyze the correlation between SVEP1 expression level and body mass index(BMI),fat mass,fat percentage and waist circumference.3T3-L1 preadipocytes and human stromal vascular fraction(SVF)cells were differentiated into mature adipocytes respectively.The expression of Svep1 in adipocytes stimulated by rosiglitazone and Forskolin was detected by realtime quantitative PCR(qRT-PCR).Based on the Pearson correlation coefficient(r>0.4,P<0.05)between RPKM values of SVEP1 and other genes in the RNA-seq database of human SAT,co-expressed gene set was screened and KEGG enrichment analysis was performed.Svep1 was knocked down in mouse primary adipocytes by lentivirus-mediated shRNA.qRT-PCR and Western blotting were used to assess the expression of thermogenic genes and proteins in adipocytes.Glycerol detection kit was used to detect the level of lipolysis stimulated by isoproterenol(ISO),and Western blotting was used to detect the phosphorylation level of lipolysis-related proteins.Results:The expression level of SVEP1 in human abdominal SAT was positively correlated with obesity related indicators(BMI,fat mass,fat percentage and waist circumference).Cold stimulation could down-regulate Svep1 transcription level in brown and beige adipocytes in mice.The transcription level of Svep1 was down-regulated in mature 3T3-L1 adipocytes and human adipocytes when stimulated by Rosi or Forskolin.KEGG enrichment analysis showed that Svep1 co-expressed gene set was enriched in the regulation of lipolysis and insulin resistance related pathways.Svep1 knockdown could significantly promote ISO-stimulated lipolysis in mouse white adipocytes and increase the expression of thermogenic genes(Ucp1,Dio2,Pgc1α,Elovl3 and Cidea)in mouse beige adipocytes.Conclusion:This study demonstrated an association between Svep1 expression and adipocyte function,and it may be implicated that Svep1 might be involved in obesity-related adipose tissue dysfunction and contribute to the development and progression of obesity.关键词
Svep1/脂肪细胞/脂解/产热/肥胖Key words
Svep1/adipocytes/lipolysis/thermogenesis/obesity分类
医药卫生引用本文复制引用
李文菲,苏莹莹,孙京京,叶雅芬,陆旭红,杨颖..细胞外基质蛋白SVEP1对脂肪细胞脂解及产热功能的影响[J].江苏大学学报(医学版),2025,35(6):487-495,9.基金项目
国家自然科学基金资助项目(82270906) (82270906)