A novel screening approach for identifying key genes involved in the regulation of brown adipose tissue thermogenesis
10.20039/j.cnki.1007-3949.2025.09.002
- VernacularTitle:调控棕色脂肪产热关键基因的新筛选方法
- Author:
Shengwen WANG
1
;
Wenbin TANG
1
;
Junxiao SHI
1
;
Weiping ZHANG
1
;
Chunchun WEI
1
Author Information
1. 海军军医大学基础医学院病理生理学教研室,上海市 200433
- Publication Type:Journal Article
- Keywords:
brown adipose tissue;
obesity;
bioinformatics analysis
- From:
Chinese Journal of Arteriosclerosis
2025;33(9):745-753
- CountryChina
- Language:Chinese
-
Abstract:
Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.
