title: Histone Demethylase LSD1 Promotes Adipocyte Differentiation through Repressing Wnt Signaling.
abstract: Adipose tissue plays important roles in animals. White fat stores energy in lipids, while brown fat is responsible for nonshivering thermogenesis through UCP1-mediated energy dissipation. Although epigenetic mechanisms modulate differentiation in multiple lineages, the epigenetic regulation of brown adipocyte differentiation is poorly understood. By screening a collection of epigenetic compounds, we found that Lysine-Specific Demethylase 1 (LSD1) inhibitors repress brown adipocyte differentiation. RNAi-mediated Lsd1 knockdown causes a similar effect, which can be rescued by expression of wild-type but not catalytic-inactive LSD1. Mechanistically, LSD1 promotes brown adipogenesis by demethylating H3K4 on promoter regions of Wnt signaling components and repressing the Wnt pathway. Furthermore, deletion of Lsd1 in mice leads to inhibition of brown adipogenesis, validating the pivotal role of LSD1 in brown fat development in vivo. Our work identifies LSD1 as a key epigenetic regulator in brown adipogenesis. The link between LSD1 and the Wnt pathway provides potential opportunities to modulate brown fat differentiation.
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Jeesun
authors.initials: J
authors.lastname: Kim
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Fang
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Zhui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Teng
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ge
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: Peter
authors.initials: P
authors.lastname: Atadja
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
authors.forename: En
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
authors.forename: Taiping
authors.initials: T
authors.lastname: Chen
authors.affiliation: China Novartis Institutes for BioMedical Research, 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China. Electronic address: vicky.qi@novartis.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060449:Wnt Signaling Pathway
chemical_list: D056466:Histone Demethylases; C504076:KDM1a protein, mouse