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

• Published in: iScience 2023-05, Vol.26 (5), p.106552-106552, Article 106552
• Main Authors: Chen, Na, Yuan, Mingyang, Zhang, NingNing, Chen, Maopei, Liu, Ruixin, Wang, Jiqiu, Lu, Peng
• Format: Article
• Language: English
• Subjects: Cell biology; Human metabolism
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106552

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, β-catenin (encoded by Ctnnb1) inhibited thermogenic genes expression in differentiated beige adipocytes and repressed Ucp1 expression at transcription level. Transcriptome analysis 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 proposed that intervention of β-catenin in adipocytes could be an effective strategy to enhance energy expenditure and improve age-related metabolic performance. [Display omitted] •Ctnnb1 deficiency in UCP1-positive adipocytes promotes browning of WAT•β-catenin inhibits thermogenic genes expression in beige adipocytes•50-week-old UBKO mice have improved metabolic performance Human metabolism; Cell biology