Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk, 38453, Republic of Korea.
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, 25601, Republic of Korea.
Mol Cell Endocrinol. 2020 Apr 15;506:110757. doi: 10.1016/j.mce.2020.110757. Epub 2020 Feb 10.
SPARC, also known as osteonectin, is well known for its physiological roles in bone formation and tissue remodeling, as well as in cancer pathology; however, evidence regarding its function in adipocytes is lacking. The present study explored the physiological role of SPARC in cultured 3T3-L1 white and HIB1B brown adipocytes of murine cell lines. Treatment of recombinant SPARC upregulated the fat browning marker proteins and genes in white adipocytes and activated brown adipocytes. Conversely, knockdown of Sparc markedly reduced these genes and proteins in both cell lines. In addition, recombinant SPARC inhibited expression of adipogenic and lipogenic proteins but elevated lipolytic and fatty acid oxidation proteins. Furthermore, in silico analysis revealed that SPARC directly interacted and regulated VEGF in adipocytes. In conclusion, SPARC acts as a regulatory protein in both white and brown adipocytes by controlling thermogenesis and is thus regarded as a possible therapeutic target for treatment of obesity.
富含半胱氨酸的酸性分泌蛋白（SPARC），又被称为骨连接蛋白，其在骨骼形成和组织重塑以及癌症病理生理学方面的生理作用已得到充分证实；然而，关于其在脂肪细胞中的功能却知之甚少。本研究旨在探讨 SPARC 在培养的 3T3-L1 白色和 HIB1B 棕色脂肪细胞中的生理作用。重组 SPARC 的处理可上调白色脂肪细胞中脂肪棕色标记蛋白和基因，并激活棕色脂肪细胞。相反，Sparc 的敲低显著降低了这两种细胞系中这些基因和蛋白的表达。此外，重组 SPARC 抑制了脂肪生成和脂生成蛋白的表达，但提高了脂肪分解和脂肪酸氧化蛋白的表达。此外，计算机模拟分析表明，SPARC 可直接相互作用并调节脂肪细胞中的血管内皮生长因子（VEGF）。综上所述，SPARC 通过控制产热来作为白色和棕色脂肪细胞中的调节蛋白发挥作用，因此被认为是治疗肥胖的潜在治疗靶点。
