BMP4-stimulated angiogenesis and adipogenesis contribute to adipocytes recruitment in subcutaneous white adipose tissue during beiging
作者单位：Key Laboratory of Metabolism and Molecular Medicine the Ministry of Education
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议》
会议日期：2014年
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术]
关 键 词：BMP4 adipogenesis angiogenesis WAT BAT
摘 要：Adipose tissues are important organs for energy homeostasis. White adipose tissue(WAT)stores energy in the form of triglycerides, whereas brown adipose tissue(BAT) dissipatesenergy in the form of heat. Adipose tissue expands to accommodate changes in energyavailability through hypertrophy of existing adipocytes and by initiating adipogenic differentiationof stem cells. Accumulation of visceral WAT is associated with adverse metabolicoutcomes, whereas increased amounts of subcutaneous WAT has been viewed as beneficialin its metabolic effects. WAT, especially in some subcutaneous depots will undergo‘beiging’- the process of acquiring characteristics of BAT- following cold exposure ortreatment with adrenergic activators or antidiabetic drugs, thiazolidinediones. De novoadipogeneis of subcutaneous WAT is evidenced during ‘beiging’ after cold exposure,which is accompanied by switching on an angiogenesis. However, the mechanisms bywhich adipogenesis is coordinated angiogeneis are largely unknown. Our previous workshowed BMP4 acquires subcutaneous WAT with BAT activity(beiging) along with increasednumber of both stromal vascular cells and mature adipocytes, indicating thatBMP4 both recruits and activates the beige adipocytes. In the present study, we found increasednumber of vascular endothelia in subcutaneous WAT of transgenic mice overexpressingBMP4, and decreased of that in knockouts. In ex vivo angiogenesis assay, sproutingfrom adipose tissue fragement was enhanced in tissues taken from BMP4 transgenicmice, or directly stimulated by BMP4 treatment. EdU labeling study detected EdU positivecells in both stromal vascular and mature adipocyte fraction of subcutaneous WAT, andthat was increased in mature adipocytes from transgenic mice, indicating BMP4 stimulatedstem cells proliferation as well as adipogenic differentiation. PDGFRβ positive pericytesaround blood microvessels were further evidenced to be the cell population regulated byBMP4, as most of the EdU positive SVF c