Abstract
Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis.
Highlights
Adult adipose tissue contains adipocyte progenitors that are critical to adipose homeostatic turnover as well as adaptive hyperplastic expansion and regeneration [1,2,3,4]
Fluorescence-activated cell sorting (FACS) analysis indicated that a small percentage of the stromal vascular fraction (SVF) cells, which expressed fibroblast markers α-smooth muscle actin (αSMA) and vimentin (S1C and S1D Fig), expressed tdTomato (Fig 1A)
cluster of differentiation 34 (CD34)+stem cell antigen-1 (Sca1)+ preadipocytes were enriched in the tdTomato−, but not the tdTomato+, SVF populations (Fig 1D and S1E Fig)
Summary
Adult adipose tissue contains adipocyte progenitors that are critical to adipose homeostatic turnover as well as adaptive hyperplastic expansion and regeneration [1,2,3,4]. Peroxisome proliferator-activated receptor-γ (PPARγ)+ adipocyte progenitors and preadipocytes— characteristic of cell surface markers, e.g., cluster of differentiation 34 (CD34) and stem cell antigen-1 (Sca1)—reside in the adipose vasculature expressing mural cell markers α-smooth muscle actin (αSMA), platelet-derived growth factor receptor-β (PDGFR-β), and neural glial antigen 2 (NG2) [1,2,5,6]. Stromal vascular fraction (SVF)-resident preadipocytes are highly committed and are capable of proliferating and differentiating into mature adipocytes in vitro and in vivo [1,2,3]. Wnt signaling plays crucial roles during development [7]. Activation of β-catenin-dependent canonical Wnt signaling in the preadipocytes inhibits adipogenesis [5,8,9]
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