Ctnnb1/beta-catenin inactivation in UCP1-positive adipocytes augments the browning of white adipose tissue

作者

Chen, N; Yuan, MY; Zhang, NN; Chen, MP; Liu, RX; Wang, JQ; Lu, P

作者单位

[Chen, Na; Yuan, Mingyang; Zhang, NingNing; Chen, Maopei; Wang, Jiqiu] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Shanghai Inst Endocrine & Metab Dis,Dept Endocrine, Shanghai 200025, Peoples R China; [Chen, Na; Yuan, Mingyang; Zhang, NingNing; Liu, Ruixin; Wang, Jiqiu] Shanghai Natl Ctr Translat Med, Shanghai Natl Clin Res Ctr Metab Dis, Key Lab Endocrine & Metab Dis Natl Hlth Commiss PR, Shanghai 200025, Peoples R China; [Chen, Maopei] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China; [Chen, Maopei] Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai 200032, Peoples R China; [Lu, Peng] Shandong First Med Univ, Shandong Prov Hosp, Dept Endocrinol, Jinan 250021, Shandong, Peoples R China

摘要

Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific Ctnnb1 knockout mice (UBKO) and observed increased "browning"of white adipose tissue (WAT) following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure. Furthermore, 0-catenin (encoded by Ctnnb1) inhibited thermogenic genes expression in differentiated beige adipo-cytes and repressed Ucp1 expression at transcription level. Transcriptome anal-ysis revealed UBKO mice treated with CL-316,243 had enhanced mitochondrial function and downregulated immune-related genes in epididymal WAT. Improved glucose tolerance and insulin sensitivity were observed in 50 -week-old UBKO mice. Public datasets indicated that CTNNB1 expression was inversely correlated with several thermogenic genes expression in human adipose tissue/ adipocytes and positively correlated with BMI or waist-hip ratio (WHR). We pro-posed that intervention of 0-catenin in adipocytes could be an effective strategy to enhance energy expenditure and improve age-related metabolic performance.

关键词

基本信息

所属机构:

归属医师: 芦鹏

UT：000999976700001

刊名:ISCIENCE

年，卷(期):2023年26卷5期

页码：-null

DOI：10.1016/j.isci.2023.106552

附件：

收录: SCIE