Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes
Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes
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DOI：
10.2337/db14-1932
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发表时间：
2015-12-01
期刊：
影响因子：
7.7
通讯作者：
Wolfrum, Christian
中科院分区：
文献类型：
--
作者：
Challa, Tenagne D.;Straub, Leon G.;Wolfrum, Christian
有许多已知的脂肪因子差异分泌的不同脂肪库，然而，他们的旁分泌和自分泌的从头脂肪细胞形成的影响还没有完全了解。通过建立前脂肪细胞与原代皮下和内脏脂肪细胞或组织块共培养的方法，我们可以证明总分泌组抑制前脂肪细胞的分化。使用蛋白质组学方法与分级分泌组样本，我们能够确定一系列的因素，无论是积极或消极影响脂肪细胞的形成。在分泌的因子中，Slc 27 a1、Vim、Cp和Ecm 1促进脂肪细胞分化，而Got 2、Cpq、白细胞介素-1受体样1/ST 2-IL-33、Sparc和Lgals 3bp降低脂肪细胞分化。在瘦型受试者、肥胖受试者和肥胖2型糖尿病受试者的人皮下脂肪细胞中，Vim和Slc 27 a1表达与脂肪细胞大小和BMI呈负相关，与胰岛素敏感性呈正相关，而Sparc和Got 2则表现出相反的趋势。此外，我们证明了Slc 27 a1在病态肥胖患者体重减轻后增加，而Sparc表达减少。总而言之，我们的研究结果确定了通过正或负旁分泌和自分泌反馈循环机制调节脂肪细胞分化的脂肪因子，这可能会影响全身能量代谢。
There are many known adipokines differentially secreted from the different adipose depots; however, their paracrine and autocrine effects on de novo adipocyte formation are not fully understood. By developing a coculture method of preadipocytes with primary subcutaneous and visceral adipocytes or tissue explants, we could show that the total secretome inhibited preadipocyte differentiation. Using a proteomics approach with fractionated secretome samples, we were able to identify a spectrum of factors that either positively or negatively affected adipocyte formation. Among the secreted factors, Slc27a1, Vim, Cp, and Ecm1 promoted adipocyte differentiation, whereas Got2, Cpq, interleukin-1 receptor-like 1/ST2-IL-33, Sparc, and Lgals3bp decreased adipocyte differentiation. In human subcutaneous adipocytes of lean subjects, obese subjects, and obese subjects with type 2 diabetes, Vim and Slc27a1 expression was negatively correlated with adipocyte size and BMI and positively correlated with insulin sensitivity, while Sparc and Got2 showed the opposite trend. Furthermore, we demonstrate that Slc27a1 was increased upon weight loss in morbidly obese patients, while Sparc expression was reduced. Taken together, our findings identify adipokines that regulate adipocyte differentiation through positive or negative paracrine and autocrine feedback loop mechanisms, which could potentially affect whole-body energy metabolism.