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J Mol Cell Biol. 2016 Aug;8(4):302-12. doi: 10.1093/jmcb/mjw019. Epub 2016 Mar 29.

BMP4 mediates the interplay between adipogenesis and angiogenesis during expansion of subcutaneous white adipose tissue.

Author information

1
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.
2
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.
3
Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.

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.

KEYWORDS:

BMP4; PDGFRβ; adipogenesis; adipose stem cells; angiogenesis

PMID:
27030507
DOI:
10.1093/jmcb/mjw019
[Indexed for MEDLINE]

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