Effects of orexin A on GLUT4 expression and lipid content via MAPK signaling in 3T3-L1 adipocytes
Effects of orexin A on GLUT4 expression and lipid content via MAPK signaling in 3T3-L1 adipocytes
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DOI：
10.1016/j.jsbmb.2013.07.005
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
Yang Shen;Yuyan Zhao;D. Zheng;X. Chang;S. Ju;Lei Guo
中科院分区：
文献类型：
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作者：
Yang Shen;Yuyan Zhao;D. Zheng;X. Chang;S. Ju;Lei Guo
食欲素A调节食物摄入、能量代谢和胃肠道功能;它还增加葡萄糖摄取并抑制脂解，表明食欲素A在葡萄糖和脂质代谢中的作用。本研究探讨了食欲素A对3 T3-L1前脂肪细胞和脂肪细胞葡萄糖转运蛋白4（GLUT 4）mRNA水平和脂质含量的影响。在正常和肥胖大鼠的脂肪组织中测定食欲素受体1（OX 1 R）蛋白表达。此外，3 T3-L1前脂肪细胞和分化的3 T3-L1脂肪细胞与不同浓度的食欲素A（10− 9至10− 7 M）孵育，无或有OX 1 R特异性拮抗剂，然后分析过氧化物酶体增殖物激活受体-γ2（PPARγ2）mRNA表达。将分化的3 T3-L1脂肪细胞暴露于orexin A，不加或加MAPK和OX 1 R拮抗剂，之后测量GLUT 4和ERK 1/2、JNK和p38 MAPK活化以及甘油三酯（TG）含量。我们观察到OX 1 R蛋白在肥胖大鼠中表达减少，并且OX 1 R蛋白水平与体脂、Lee's指数、TG、总胆固醇和空腹胰岛素水平呈负相关。Orexin A通过OX 1 R以剂量依赖方式促进3 T3-L1前脂肪细胞中PPARγ2 mRNA的表达。在分化的3 T3-L1脂肪细胞中，食欲素A显著增加GLUT 4 mRNA水平，这被ERK 1/2、JNK和p38 MAPK抑制剂以及OX 1 R拮抗剂阻断。此外，食欲素A通过ERK 1/2、JNK和p38 MAPK以及OX 1 R增加细胞TG含量。因此，食欲素A通过ERK 1/2、JNK和p38 MAPK信号传导增加分化的3 T3-L1脂肪细胞中的GLUT 4 mRNA表达和脂质积累。此外，食欲素A增加3 T3-L1前脂肪细胞中的PPARγ2 mRNA表达。进一步的研究是必要的，以阐明食欲素A在代谢紊乱和脂肪细胞分化的影响。
Orexin A regulates food intake, energy metabolism and gastrointestinal function; it also increases glucose uptake and inhibits lipolysis, suggesting a role for orexin A in glucose and lipid metabolism. In this study, the effects of orexin A on glucose transporter 4 (GLUT4) mRNA level and lipid content were explored in 3T3-L1 preadipocytes and adipocytes. Orexin receptor 1 (OX1R) protein expression was determined in the adipose tissue of normal and obese rats. In addition, 3T3-L1 preadipocytes and differentiated 3T3-L1 adipocytes were incubated with different concentrations of orexin A (10−9to 10−7M), without or with OX1R specific antagonist, then the peroxisome proliferator-activated receptor-γ2 (PPARγ2) mRNA expression was analyzed. Differentiated 3T3-L1 adipocytes were exposed to orexin A, without or with MAPK and OX1R antagonist, after which the GLUT4 and ERK1/2, JNK, and p38 MAPK activation, and triglyceride (TG) content were measured. We observed that OX1R protein expression was decreased in obese rats, and OX1R protein level was negatively correlated with body fat, Lee's index, TG, total cholesterol, and fasting insulin levels. Orexin A enhanced PPARγ2 mRNA expression in a dose-dependent manner in 3T3-L1 preadipocytes through OX1R. In differentiated 3T3-L1 adipocytes, orexin A significantly increased GLUT4 mRNA levels, which was blocked by the ERK1/2, JNK, and p38 MAPK inhibitors as well as OX1R antagonist. Furthermore, orexin A increased cellular TG content via ERK1/2, JNK, and p38 MAPK as well as OX1R. Thus, orexin A increases GLUT4 mRNA expression and lipid accumulation in differentiated 3T3-L1 adipocytes via ERK1/2, JNK, and p38 MAPK signaling. In addition, orexin A increases PPARγ2 mRNA expression in 3T3-L1 preadipocytes. Further studies are necessary to elucidate the impact of orexin A in metabolic disorders and adipocyte differentiation.