Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA.
Adipocyte. 2021 Dec;10(1):574-586. doi: 10.1080/21623945.2021.1987634.
Expansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of in mice results in disproportionate postnatal growth of gonadal WAT (gWAT), while iWAT and BAT were similar in size between KO and WT mice. deficiency increased the number of PDGFRa+ stromal vascular fraction (SVF) cells in gWAT and showed increased proliferation and fibrosis. KO gWAT had increased collagen deposition and elevated expression of markers of inflammation. In vitro, SPRY1 was transiently down regulated during early adipocyte differentiation of SVF cells, with levels increasing at later stages of differentiation. SPRY1 deficiency enhances PDGF-AA and PDGF-BB induced proliferation of SVF cells. Increased proliferation of SVF from KO gWAT accompanies an increase in AKT activation. PDGF-AA stimulated a transient down regulation of SPRY1 in wild type SVF, whereas PDGF-BB stimulated a sustained down regulation of SPRY1 in wild type SVF. Collectively, our data suggest that SPRY1 is critical for regulating postnatal growth of gWAT by restraining APC proliferation and differentiation in part by regulation of PDGFRa/b-AKT signaling.
内脏白色脂肪组织（vWAT）的扩张是对营养过剩的反应，也是代谢疾病的风险因素。SPRY1 是一种受体酪氨酸激酶（RTK）信号的反馈抑制剂，在体内表达于 PDGFRa+脂肪细胞祖细胞（APC）中。在小鼠中， 基因的全局缺失导致生殖腺 WAT（gWAT）在出生后不成比例地生长，而 iWAT 和 BAT 在 KO 和 WT 小鼠之间的大小相似。 基因缺失增加了 gWAT 中 PDGFRa+基质血管部分（SVF）细胞的数量，并显示出增殖和纤维化增加。KO gWAT 有增加的胶原蛋白沉积和炎症标志物的表达增加。在体外，SVF 细胞早期脂肪细胞分化过程中 SPRY1 短暂下调，分化后期水平增加。SPRY1 缺失增强了 SVF 细胞对 PDGF-AA 和 PDGF-BB 的增殖反应。KO gWAT 的 SVF 增殖增加伴随着 AKT 激活的增加。PDGF-AA 刺激野生型 SVF 中 SPRY1 的短暂下调，而 PDGF-BB 刺激野生型 SVF 中 SPRY1 的持续下调。总之，我们的数据表明，SPRY1 通过抑制 APC 的增殖和分化来调节 gWAT 的出生后生长，部分通过调节 PDGFRa/b-AKT 信号通路。
