Zhang Min, Wang Bin, Ni Yu-Hui, Liu Feng, Fei Li, Pan Xiao-qing, Guo Mei, Chen Rong-hua, Guo Xi-rong
Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, 210004 Nanjing, China.
Life Sci. 2006 Sep 5;79(15):1428-35. doi: 10.1016/j.lfs.2006.04.012. Epub 2006 Apr 27.
Uncoupling proteins are a family of mitochondrial proteins involved in energy metabolism. We previously showed that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats. However, the effect of UCP4 on adipocytes is unclear. In this work, we established a stable preadipocyte cell line overexpressing UCP4 to observe the direct effect of UCP4 on adipocytes. Cells overexpressing UCP4 showed significantly attenuated differentiation of preadipocytes into adipocytes. During differentiation, expression of adipogenesis-associated markers such as fatty acid synthetase, peroxisome proliferator-activated receptor gamma, CCAAT enhancer binding protein alpha, adipocyte lipid binding protein and lipoprotein lipase were downregulated. Preadipoctes expressing UCP4 grew faster and more of them stayed in S phase compared to control cells. In addition, UCP4 overexpression protected preadipocytes from apoptosis induced by serum deprivation. Our results demonstrate that overexpression of UCP4 can promote proliferation and inhibit apoptosis and differentiation of preadipocytes.
解偶联蛋白是参与能量代谢的一类线粒体蛋白。我们之前发现，在饮食诱导的肥胖大鼠和正常大鼠的网膜脂肪组织中，解偶联蛋白4（UCP4）存在差异表达。然而，UCP4对脂肪细胞的作用尚不清楚。在本研究中，我们建立了一个稳定过表达UCP4的前脂肪细胞系，以观察UCP4对脂肪细胞的直接作用。过表达UCP4的细胞显示前脂肪细胞向脂肪细胞的分化显著减弱。在分化过程中，脂肪酸合成酶、过氧化物酶体增殖物激活受体γ、CCAAT增强子结合蛋白α、脂肪细胞脂质结合蛋白和脂蛋白脂肪酶等脂肪生成相关标志物的表达下调。与对照细胞相比，表达UCP4的前脂肪细胞生长更快，更多细胞停留在S期。此外，UCP4过表达可保护前脂肪细胞免受血清剥夺诱导的凋亡。我们的结果表明，UCP4过表达可促进前脂肪细胞的增殖并抑制其凋亡和分化。
