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作者

Na Chen Mingyang Yuan NingNing Zhang Maopei Chen Ruixin Liu Jiqiu Wang Peng Lu

作者单位

⁵Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong 250021, China ¹Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China ⁴Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China ³These authors contributed equally ⁶Lead contact ²Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Shanghai 200025, China

刊名

iScience

年份

2023

卷号

Vol.26 No.5

页码

106552

ISSN

2589-0042

关键词

β-catenin UCP1 thermogenesis beige adipocytes energy expenditure

摘要

Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific Ctnnb1 knockout mice and observed increased “browning” of white adipose tissue following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure. Furthermore, β-catenin inhibited thermogenic genes expression in differentiated beige adipocytes and repressed Ucp1 expression at transcription level. Transcrip...更多

Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific Ctnnb1 knockout mice and observed increased “browning” of white adipose tissue following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure. Furthermore, β-catenin 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 body mass index or waist-hip ratio . We proposed that intervention of β-catenin in adipocytes could be an effective strategy to enhance energy expenditure and improve age-related metabolic performance.收起

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