title: BMP4 mediates the interplay between adipogenesis and angiogenesis during expansion of subcutaneous white adipose tissue.
abstract: The expansion of subcutaneous (SC) white adipose tissue (WAT) has beneficial effects on metabolic health. Our previous work showed an increased number of bone morphogenetic protein 4 (BMP4)-activated beige adipocytes in SC WAT, indicating a potential role of BMP4 in adipocyte recruitment. It was also demonstrated that BMP4 committed multipotent mesodermal C3H10T1/2 stem cells to the adipocyte lineage ex vivo However, the mechanism by which BMP4 regulates adipogenesis in vivo has not been clarified. In this study, we found that BMP4 stimulated de novo adipogenesis in SC WAT concomitant with enhanced blood vessel formation, thus promoting adipose tissue angiogenesis. Platelet-derived growth factor receptor-β-positive (PDGFRβ(+)) multipotent stem cells within the neoangiogenic vessels were found to be adipocyte progenitors. Moreover, BMP4 downregulated PDGFRβ by stimulating the lysosome-dependent degradation, which efficiently initiated adipogenic differentiation. These results suggest how BMP4 regulates adipocyte recruitment in SC WAT, and thus promote its beneficial metabolic effects.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China qqtang@shmu.edu.cn shuwenqian2013@163.com.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Qian
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Meng-Yuan
authors.initials: MY
authors.lastname: Wu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.
authors.forename: Cong-Jian
authors.initials: CJ
authors.lastname: Xu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China qqtang@shmu.edu.cn shuwenqian2013@163.com.
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D007264:Inguinal Canal / Q000033:anatomy & histology; D008247:Lysosomes / Q000378:metabolism; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000378:metabolism; D059748:Proteolysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D050151:Subcutaneous Fat / Q000254:growth & development* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D055415:Bone Morphogenetic Protein 4; D016207:Cytokines; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: BMP4; PDGFRβ; adipogenesis; adipose stem cells; angiogenesis