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首页> 中文期刊> 《中国比较医学杂志》 >蛋白磷酸酶5（PP5）对小鼠脂肪代谢的影响

蛋白磷酸酶5（PP5）对小鼠脂肪代谢的影响

         
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Objective To investigate the effect of protein phosphatase 5 (PP5) on lipid metabolism in the PP5 knockout (KO) mice.Methods Male PP5 KO and wild type (WT) mice at the age of 6 weeks were used in this study. In order to study the effect of high fat diet ( HFD) feeding, the body weight was measured.The liver histology was examined by HE and oil red O staining.To further verify PP5 functions in the adipogenesis, in vitro experiment was carried out using mouse embryonic fibroblasts (MEF).Western blotting and real-time PCR were performed to quantified the expression of lipid metabolism-related genes in the liver tissues.Results Compared with the WT mice, the body weight gain was slower in the KO mice.The size of the lipid droplets was smaller and the quantity was less in the KO mouse liver tissue.In vitro study revealed that the KO mouse MEF cells showed less differentiated adipocytes with smaller lipid droplets than the WT MEF cells.This observation was further confirmed by detecting the expression of adipogenesis-related genes in the HFD liver.The markers of adipocyte differentiation, such as CD36, AP2, PPARγ2, and Glut4, were significantly decreased, while energy expenditure-related markers, such as phosphorylation of GR and expression of UCP1, were significantly increased.Conclusions Protein phosphatase 5 may play a regulatory role in the mouse lipid metabolism through regulating the de-phosphorylation of p-GR and enhancing the expression of UCP1.%目的：利用蛋白磷酸酶5（PP5）基因敲除小鼠，探究 PP5在小鼠脂肪代谢中的作用。方法随机选取6周龄雄性 PP5基因敲除（PP5 KO）和野生型（WT）小鼠，高脂饲养6周后，应用 HE 染色和油红 O 染色技术对小鼠肝脏结构和脂滴积累进行检测，应用 Western blotting 和 real－time PCR 技术检测肝脏组织中脂代谢相关基因的表达情况。同时应用 PP5 KO 和 WT 小鼠成纤维细胞，在体外观察 PP5对脂肪分化的影响。结果与 WT 小鼠相比，高脂饲养后 PP5 KO 小鼠体重与 WT 小鼠相比显著减轻，肝脏中脂滴数量显著较少且脂滴较小。体外实验发现与 WT 小鼠胚胎成纤维细胞（mouse embryonic fibroblast，MEF）相比 PP5 KO MEF 细胞脂肪分化显著较弱，脂滴较小。此外，在 PP5 KO 肝脏组织中脂肪分化标记基因 CD36、AP2、PPARγ2和 Glut4的相对表达量显著降低，而能量代谢相关蛋白糖皮质激素受体（GR）的磷酸化水平显著增加，解偶联蛋白1（UCP1）表达量也显著升高。结论 PP5通过调节 GR 的去磷酸化影响机体脂肪分化和能量代谢调控小鼠脂肪代谢。

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