Meissburger Bettina, Perdikari Aliki, Moest Hansjörg, Müller Sebastian, Geiger Matthias, Wolfrum Christian
Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Institute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Biochim Biophys Acta. 2016 Sep;1861(9 Pt A):1121-1131. doi: 10.1016/j.bbalip.2016.06.010. Epub 2016 Jun 16.
Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to the development of metabolic dysfunction. We show here that adipocyte differentiation in subcutaneous stromal-vascular fraction (SVF) is increased compared to visceral SVF, however this increased differentiation capacity seems not to be due to changes in the number of adipocyte precursor cells. Rather, we demonstrate that secreted heat-sensitive factors from the SVF can inhibit adipocyte differentiation and that this effect is higher in visceral than in subcutaneous SVF, suggesting that visceral SVF is a source of secreted factors that can inhibit adipocyte formation. In order to explore secreted proteins that potentially inhibit differentiation in visceral preadipocytes we analyzed the secretome of both SVFs which led to the identification of 113 secreted proteins with an overlap of 42%. Further expression analysis in both depots revealed 16 candidates that were subsequently analyzed in a differentiation screen using an adenoviral knockdown system. From this analysis we were able to identify two potential inhibitory candidates, namely decorin (Dcn) and Sparc-like 1 (Sparcl1). We could show that ablation of either candidate enhanced adipogenesis in visceral preadipocytes, while treatment of primary cultures with recombinant Sparcl1 and Dcn blocked adipogenesis in a dose dependent manner. In conclusion, our data suggests that the differences in adipogenesis between depots might be due to paracrine and autocrine feedback mechanisms which could in turn contribute to metabolic homeostasis.
内脏和皮下脂肪组织库具有不同的特征，对代谢功能障碍的发展贡献各异。我们在此表明，与内脏基质血管组分（SVF）相比，皮下SVF中的脂肪细胞分化增加，然而这种增加的分化能力似乎并非由于脂肪细胞前体细胞数量的变化。相反，我们证明SVF分泌的热敏感因子可抑制脂肪细胞分化，且这种作用在内脏SVF中比在皮下SVF中更强，这表明内脏SVF是可抑制脂肪细胞形成的分泌因子的来源。为了探索可能抑制内脏前脂肪细胞分化的分泌蛋白，我们分析了两种SVF的分泌蛋白组，从而鉴定出113种分泌蛋白，重叠率为42%。在两个脂肪组织库中的进一步表达分析揭示了16个候选蛋白，随后使用腺病毒敲低系统在分化筛选中对其进行了分析。通过该分析，我们能够鉴定出两个潜在的抑制性候选蛋白，即核心蛋白聚糖（Dcn）和类腱生蛋白1（Sparcl1）。我们可以证明，敲除任一候选蛋白均可增强内脏前脂肪细胞的脂肪生成，而用重组Sparcl1和Dcn处理原代培养物则以剂量依赖方式阻断脂肪生成。总之，我们的数据表明，不同脂肪组织库之间脂肪生成的差异可能归因于旁分泌和自分泌反馈机制，这反过来可能有助于代谢稳态。
