Choy L N, Spiegelman B M
Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Obes Res. 1996 Nov;4(6):521-32. doi: 10.1002/j.1550-8528.1996.tb00266.x.
Adipose tissue is a major source of adpisin/factor D of the alternative pathway of complement. Adipose tissue also expresses the two other complement components which are involved in the first activation step of the alternative pathway, factor B and C3, and this step is activated in adipose tissue, producing C3a/Acylation Stimulating Protein (C3a/ASP), a stimulator of triglyceride synthesis. Complement activation is a highly regulated process, however, nothing is known about regulation of complement activation in adipose tissue. To gain insight into the nature of adipose complement activation and its regulation, we have now examined the expression of several complement activation regulatory genes, and analyzed the production of C3a/ASP in lean vs. obese, adpisin-deficient mice. We found that undifferentiated preadipocytes expressed the mRNAs encoding the negative regulatory proteins Crry and factor H, but expression of both genes was decreased upon differentiation. The positive regulator properdin, as well as Crry and factor H, were found in adipose tissue. None of these genes was regulated in murine genetic obesity. To investigate the relative levels of complement activation in lean vs. adpisin-deficient obese mice, we developed a radioimmunoassay for measurement of murine C3a/ASP in plasma. We report that there was no significant difference in the level of C3a in lean vs. obese plasma; however, we found a positive correlation between C3a and plasma triglyceride levels in normal lean mice.
脂肪组织是补体替代途径中脂联素/因子D的主要来源。脂肪组织还表达参与替代途径第一步激活的另外两种补体成分，即因子B和C3，且该步骤在脂肪组织中被激活，产生甘油三酯合成的刺激物C3a/酰化刺激蛋白（C3a/ASP）。补体激活是一个高度受调控的过程，然而，关于脂肪组织中补体激活的调控情况却一无所知。为深入了解脂肪组织补体激活的本质及其调控机制，我们现在检测了几种补体激活调节基因的表达，并分析了瘦型与肥胖型、脂联素缺陷型小鼠中C3a/ASP的产生情况。我们发现未分化的前脂肪细胞表达编码负调控蛋白Crry和因子H的mRNA，但在分化后这两个基因的表达均降低。在脂肪组织中发现了正调控因子备解素以及Crry和因子H。在小鼠遗传性肥胖中，这些基因均未受到调控。为研究瘦型与脂联素缺陷型肥胖小鼠中补体激活的相对水平，我们开发了一种放射免疫分析法来测量血浆中的小鼠C3a/ASP。我们报告称，瘦型与肥胖型血浆中C3a水平无显著差异；然而，我们发现正常瘦型小鼠中C3a与血浆甘油三酯水平呈正相关。
