Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Int J Mol Sci. 2018 Dec 11;19(12):3992. doi: 10.3390/ijms19123992.
Adipogenesis is a tightly regulated cellular process that involves the action of multiple signaling pathways. Characterization of regulators that are associated with adipose development is crucial to understanding the mechanisms underlying obesity and other metabolic disorders. Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that was first described as a neurotrophic factor. The role of PEDF in lipid metabolism was established when adipose triglyceride lipase (ATGL), a major triglyceride hydrolase, was characterized as its binding partner. In this study, we investigated the downstream effects of PEDF on adipogenic differentiation using rat adipose-derived stem cells (AdSCs) and the mouse pre-adipocyte cell line 3T3-L1. Knocking down PEDF in differentiating cells resulted in elevated levels of ATGL and CD36, as well as other adipogenic markers, with a concomitant increase in adipocyte number. CD36, a scavenger receptor for a variety of ligands, regulated proliferation and lipogenic gene expression during adipogenesis. The CD36 increase due to PEDF down-regulation might be a result of elevated PPARγ. We further demonstrated that PEDF expression was regulated by dexamethasone, a synthetic glucocorticoid that is widely used for adipogenesis at the transcriptional level. Taken together, our findings highlight that PEDF negatively regulates adipogenesis through the regulation of various signaling intermediates, and it may play a crucial role in lipid metabolic disorders.
脂肪生成是一个受到严格调控的细胞过程，涉及多个信号通路的作用。鉴定与脂肪发育相关的调节因子对于理解肥胖和其他代谢紊乱的机制至关重要。色素上皮衍生因子（PEDF）是一种分泌糖蛋白，最初被描述为一种神经营养因子。当脂肪甘油三酯脂肪酶（ATGL），一种主要的甘油三酯水解酶，被鉴定为其结合伴侣时，PEDF 在脂质代谢中的作用就被确定了。在这项研究中，我们使用大鼠脂肪来源的干细胞（AdSCs）和小鼠前脂肪细胞系 3T3-L1 研究了 PEDF 对脂肪生成分化的下游影响。在分化细胞中敲低 PEDF 会导致 ATGL 和 CD36 以及其他脂肪生成标志物的水平升高，同时脂肪细胞数量增加。CD36 是多种配体的吞噬受体，在脂肪生成过程中调节细胞增殖和脂生成基因表达。由于 PEDF 下调导致 CD36 增加可能是由于 PPARγ 升高所致。我们进一步证明，DEX，一种广泛用于转录水平脂肪生成的合成糖皮质激素，可调节 PEDF 的表达。总之，我们的研究结果表明，PEDF 通过调节各种信号中间物负向调节脂肪生成，它可能在脂质代谢紊乱中发挥关键作用。
