Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, PR China.
J Steroid Biochem Mol Biol. 2013 Nov;138:376-83. doi: 10.1016/j.jsbmb.2013.07.005. Epub 2013 Jul 29.
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(-9) to 10(-7)M), 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.
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肪分解，表明食欲素 A 在葡萄糖和脂质代谢中发挥作用。在这项研究中，探讨了食欲素 A 在 3T3-L1 前脂肪细胞和脂肪细胞中对葡萄糖转运蛋白 4（GLUT4）mRNA 水平和脂质含量的影响。测定了正常和肥胖大鼠脂肪组织中食欲素受体 1（OX1R）蛋白的表达。此外，用不同浓度的食欲素 A（10(-9) 到 10(-7)M）孵育 3T3-L1 前脂肪细胞和分化的 3T3-L1 脂肪细胞，而不添加或添加 OX1R 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 3T3-L1 脂肪细胞暴露于食欲素 A，而不添加或添加 MAPK 和 OX1R 拮抗剂，然后测量 GLUT4 和 ERK1/2、JNK 和 p38 MAPK 的激活以及三酰甘油（TG）含量。我们观察到肥胖大鼠中 OX1R 蛋白表达降低，OX1R 蛋白水平与体脂肪、Lee 指数、TG、总胆固醇和空腹胰岛素水平呈负相关。食欲素 A 通过 OX1R 以剂量依赖的方式增强 3T3-L1 前脂肪细胞中 PPARγ2 mRNA 的表达。在分化的 3T3-L1 脂肪细胞中，食欲素 A 显著增加 GLUT4 mRNA 水平，该作用被 ERK1/2、JNK 和 p38 MAPK 抑制剂以及 OX1R 拮抗剂阻断。此外，食欲素 A 通过 ERK1/2、JNK 和 p38 MAPK 以及 OX1R 增加细胞内 TG 含量。因此，食欲素 A 通过 ERK1/2、JNK 和 p38 MAPK 信号增加分化的 3T3-L1 脂肪细胞中 GLUT4 mRNA 的表达和脂质积累。此外，食欲素 A 增加 3T3-L1 前脂肪细胞中 PPARγ2 mRNA 的表达。需要进一步的研究来阐明食欲素 A 在代谢紊乱和脂肪细胞分化中的作用。
