Secco Blandine, Camiré Étienne, Brière Marc-Antoine, Caron Alexandre, Billong Armande, Gélinas Yves, Lemay Anne-Marie, Tharp Kevin M, Lee Peter L, Gobeil Stéphane, Guimond Jean V, Patey Natacha, Guertin David A, Stahl Andreas, Haddad Élie, Marsolais David, Bossé Yohan, Birsoy Kivanc, Laplante Mathieu
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep. 2017 Jan 3;18(1):93-106. doi: 10.1016/j.celrep.2016.12.015.
Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo. We show that VSTM2A-producing cells associate with the vasculature and express the common surface markers of adipocyte progenitors. Overexpression of VSTM2A induces adipogenesis, whereas its depletion impairs this process. VSTM2A controls preadipocyte determination at least in part by modulating BMP signaling and PPARγ2 activation. We propose a model in which VSTM2A is produced to preserve and amplify the adipogenic capability of adipose precursors.
尽管我们对调节脂肪组织发育的机制的理解取得了进展,但功能性表征脂肪前体细胞的因子的本质仍然难以捉摸。为了生成控制脂肪组织大小和功能的工具,需要确定调节脂肪细胞发育的早期步骤。在此,我们报告发现了含V结构域和跨膜结构域2A(VSTM2A),它是一种由定向前脂肪细胞表达和分泌的蛋白质。在体外脂肪生成的早期阶段和体内脂肪组织发育过程中,VSTM2A的表达均升高。我们发现产生VSTM2A的细胞与脉管系统相关,并表达脂肪细胞祖细胞的常见表面标志物。VSTM2A的过表达诱导脂肪生成,而其缺失则损害这一过程。VSTM2A至少部分地通过调节骨形态发生蛋白(BMP)信号传导和过氧化物酶体增殖物激活受体γ2(PPARγ2)的激活来控制前脂肪细胞的分化。我们提出了一个模型,即产生VSTM2A是为了维持和放大脂肪前体细胞的脂肪生成能力。