Department of Ruminant Science, Agricultural Research Organization, Rishon LeZion, Israel.
Physiol Rep. 2021 Jan;9(2):e14654. doi: 10.14814/phy2.14654.
Ghrelin and the corticotropin-releasing factor (CRF) family are known regulators of cellular metabolism and energy balance. We previously demonstrated that myoblast glucose metabolism is regulated by ghrelin and that this effect is mediated by CRF receptor type 2 (CRF-R2). Here we explored the effect of des-acyl ghrelin, the major circulating isoform of ghrelin, on cellular metabolism in mouse myoblast C2C12 cells, and examined whether CRF family receptors mediate its metabolic effects in muscle cells. C2C12 cells were exposed to des-acyl ghrelin with or without the CRF-R1- and CRF-R2-specific antagonists antalarmin or antisauvagine-30, respectively. Des-acyl ghrelin reduced glucose uptake and expression of the glucose transporter GLUT4, but induced retinol-binding protein 4 (RBP4) expression. Antalarmin and antisauvagine-30 inhibited the induction of glucose uptake by des-acyl ghrelin and its effect on GLUT4 and RBP4 expression. Moreover, treating C2C12 cells with des-acyl ghrelin resulted in cAMP activation in response to the CRF-R1-specific ligand stressin, and the CRF-R2-specific ligand Ucn3. Furthermore, des-acyl ghrelin reduced the expression of uncoupling proteins UCP2 and UCP3. Adding antalarmin or antisauvagine-30 to the medium reversed this effect. Finally, des-acyl ghrelin elevated lipid content and acetyl-CoA carboxylase expression in C2C12 cells. Our results suggest that during food deprivation, des-acyl ghrelin signals the muscle cells that glucose levels are low and that they should switch to fatty acids for their metabolic fuel.
胃饥饿素和促肾上腺皮质释放因子 (CRF) 家族是已知的细胞代谢和能量平衡调节剂。我们之前证明，成肌细胞的葡萄糖代谢受胃饥饿素调节，而这种作用是通过 CRF 受体 2（CRF-R2）介导的。在这里，我们探讨了去酰基胃饥饿素（胃饥饿素的主要循环形式）对小鼠成肌细胞 C2C12 细胞代谢的影响，并研究了 CRF 家族受体是否在肌肉细胞中介导其代谢作用。用去酰基胃饥饿素处理 C2C12 细胞，分别用 CRF-R1 和 CRF-R2 特异性拮抗剂 antalarmin 或 antisauvagine-30 处理。去酰基胃饥饿素降低葡萄糖摄取和葡萄糖转运蛋白 GLUT4 的表达，但诱导视黄醇结合蛋白 4 (RBP4) 的表达。Antalarmin 和 antisauvagine-30 抑制了去酰基胃饥饿素诱导的葡萄糖摄取及其对 GLUT4 和 RBP4 表达的影响。此外，用去酰基胃饥饿素处理 C2C12 细胞导致 cAMP 激活，对 CRF-R1 特异性配体 stressin 和 CRF-R2 特异性配体 Ucn3 有反应。此外，去酰基胃饥饿素降低了解偶联蛋白 UCP2 和 UCP3 的表达。在培养基中添加 antalarmin 或 antisauvagine-30 可逆转这种效应。最后，去酰基胃饥饿素增加了 C2C12 细胞中的脂质含量和乙酰辅酶 A 羧化酶表达。我们的结果表明，在禁食期间，去酰基胃饥饿素向肌肉细胞发出信号，表明葡萄糖水平较低，它们应该切换为脂肪酸作为代谢燃料。
