MacLaren R, Kalant D, Cianflone K
Medicine, McGill University Health Center, Montreal, Canada.
Biochem Cell Biol. 2007 Feb;85(1):11-21. doi: 10.1139/o06-207.
Acylation-stimulating protein (ASP) and interaction with its receptor C5L2 influences adipocyte metabolism. We examined insulin resistance and differentiation-mediated regulation of C5L2 and the mechanistic impact on both C5L2 cell-surface protein and ligand binding to the receptor. C5L2 mRNA increased 8.7-fold with differentiation in 3T3-L1 cells (p < 0.0001) by day 9. In preadipocytes, insulin and dexamethasone increased C5L2 mRNA (1 micromol/L insulin resulted in a 2.6-fold increase, p < 0.01; 10 nmol/L dexamethasone resulted in a 17.9-fold increase, p < 0.01) and C5L2 cell-surface protein (100 nmol insulin resulted in a 2.7-fold increase, p < 0.001; 10 nmol/L dexamethasone resulted in a 2.8-fold increase, p < 0.001). In adipocytes, 100 nmol/L insulin increased C5L2 mRNA and ASP binding (respectively, 1.3-fold, p < 0.01; and 2.4-fold, p < 0.05). Dexamethasone decreased ligand binding (-60%, p < 0.02) without changing mRNA. Tumor necrosis factor alpha decreased C5L2 mRNA (-88% in preadipocytes and -38% in adipocytes, p < 0.001), C5L2 cell-surface protein (-53% in preadipocytes, p < 0.0001), and ASP binding (-60% and -49% in, respectively, preadipocytes and adipocytes, p < 0.05). Conversely, 1 micromol/L and 10 nmol/L rosiglitazone increased, respectively, C5L2 mRNA (9.3-fold, p < 0.0001) and ASP binding (2.4-fold, p < 0.05). Thus, C5L2 mRNA increases with differentiation, insulin, and thiazolidinedione treatment, and decreases with tumor necrosis factor alpha, all of which results in functional changes in ASP-C5L2 response and may have implications for human metabolism.
酰化刺激蛋白（ASP）及其与受体C5L2的相互作用会影响脂肪细胞的代谢。我们研究了胰岛素抵抗以及C5L2的分化介导调控，以及其对C5L2细胞表面蛋白和配体与受体结合的机制性影响。在第9天时，3T3-L1细胞分化过程中C5L2 mRNA增加了8.7倍（p < 0.0001）。在脂肪前体细胞中，胰岛素和地塞米松可增加C5L2 mRNA（1微摩尔/升胰岛素导致增加2.6倍，p < 0.01；10纳摩尔/升地塞米松导致增加17.9倍，p < 0.01）和C5L2细胞表面蛋白（100纳摩尔胰岛素导致增加2.7倍，p < 0.001；10纳摩尔/升地塞米松导致增加2.8倍，p < 0.001）。在脂肪细胞中，100纳摩尔/升胰岛素增加了C5L2 mRNA和ASP结合（分别增加1.3倍，p < 0.01；以及2.4倍，p < 0.05）。地塞米松降低了配体结合（-60%，p < 0.02），但未改变mRNA。肿瘤坏死因子α降低了C5L2 mRNA（脂肪前体细胞中降低88%，脂肪细胞中降低38%，p < 0.001）、C5L2细胞表面蛋白（脂肪前体细胞中降低53%，p < 0.0001）以及ASP结合（脂肪前体细胞和脂肪细胞中分别降低60%和49%，p < 0.05）。相反，1微摩尔/升和10纳摩尔/升罗格列酮分别增加了C5L2 mRNA（9.3倍，p < 0.0001）和ASP结合（2.4倍，p < 0.05）。因此，C5L2 mRNA在分化、胰岛素和噻唑烷二酮治疗时增加，而在肿瘤坏死因子α作用下降低，所有这些都会导致ASP-C5L2反应的功能变化，可能对人体代谢产生影响。
