近日，来自瑞士的科学家在国际学术期刊diabetes上发表了一项最新研究进展，他们利用细胞共培养技术和蛋白质组学技术发现了一些可以通过旁分泌或内分泌方式调控脂肪细胞分化的脂肪因子，这对于肥胖及相关代谢综合症治疗具有一定意义。
许多研究已经发现不同部位的脂肪组织会分泌产生许多不同的脂肪因子，但是这些脂肪因子的旁分泌或自分泌对于脂肪细胞的形成具有何种影响目前仍未完全了解。
在这项研究中，研究人员开发了一种细胞共培养的方法，将脂肪前体细胞与原代的皮下脂肪，内脏脂肪细胞或组织块共同培养在一起，利用这种方法研究人员得到了一些能够调节脂肪前体细胞分化的分泌因子。
随后，他们借助蛋白组学的方法对分离得到的分泌组样品进行了分析，鉴定出了能够正向和负向调节脂肪细胞形成的不同分泌因子，在这些分泌因子中，Slc27a1，Vim，Cp以及Ecm1能够促进脂肪细胞分化，而Got2,Cpq,Il1rl1/ST-IL-33,Sparc以及Lgals3bp能够抑制脂肪细胞分化。
之后，研究人员对比较瘦的，超重以及超重并患有2型糖尿病的个体的皮下脂肪细胞进行了分析，结果发现Vim和Slc27a1的表达与脂肪细胞大小和BMI呈负相关，而与胰岛素敏感性呈正相关关系，但Sparc和Got2与前两者的趋势恰好相反。研究人员进一步研究发现肥胖病人体重减轻后Slc27a1的表达会出现增加，而Sparc的表达则会相应下降。
总的来说，这项研究发现了通过正向和负向旁分泌及内分泌反馈环机制调节脂肪细胞分化的脂肪因子，这些因子的发现对于肥胖及代谢综合征的治疗有一定启示意义。
Regulation of de novo adipocyte differentiation through crosstalk between adipocytes and pre-adipocytes
Tenagne D. Challa, Leon G. Straub, Miroslav Balaz, Elke Kiehlmann, Olivier Donze, Gottfried Rudofsky, Jozef Ukropec, Barbara Ukropcova, and Christian Wolfrum
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 co-culture method of pre-adipocytes with primary subcutaneous and visceral adipocytes or tissue explants, we could show that the total secretome inhibited pre-adipocyte differentiation. Using a proteomics approach with fractionated secretome samples, we were able to identify a spectrum of factors which either positively or negatively affected adipocyte formation. Among the secreted factors, Slc27a1, Vim, Cp and Ecm1 promoted adipocyte differentiation, wheras Got2, Cpq, Il1rl1/ST2-IL-33, Sparc, and Lgals3bp decreased adipocyte differentiation. In human subcutaneous adipocytes of lean, obese and obese/type 2 diabetic subjects, Vim andSlc27a1 expression was negatively correlated with adipocyte size and body mass index (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.