Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, North Torrey Pines Road, La Jolla, California, 10010, USA.
Obesity (Silver Spring). 2014 Feb;22(2):380-9. doi: 10.1002/oby.20535. Epub 2013 Sep 10.
Ghrelin is known to regulate appetite control and cellular metabolism. The corticotropin-releasing factor (CRF) family is also known to regulate energy balance. In this study, the links between ghrelin and the CRF family in C2C12 cells, a mouse myoblast cell line was investigated.
C2C12 cells were treated with ghrelin in the presence or absence of CRF receptor antagonists and then subjected to different metabolic analyses.
Ghrelin enhanced glucose uptake by C2C12 cells, induced GLUT4 translocation to the cell surface and decreased RBP4 expression. A CRF-R2 selective antagonist, anti-sauvagine-30, blocked ghrelin-induced glucose uptake, Ghrelin upregulated CRF-R2 but not CRF-R1 levels. Moreover, ghrelin-treated C2C12 cells displayed a cAMP and pERK activation in response to Ucn3, a CRF-R2 specific ligand, but not in response to CRF or stressin, CRF-R1 specific ligands. Ghrelin also induced UCP2 and UCP3 expression, which were blocked by anti- sauvagine-30. Ghrelin did not induce fatty acids uptake by C2C12 cells or ACC expression. Even though C2C12 cells clearly exhibited responses to ghrelin, the known ghrelin receptor, GHSR1a, was not detectable in C2C12 cells.
The results suggest that, ghrelin plays a role in regulating muscle glucose and, raise the possibility that suppression of the CRF-R2 pathway might provide benefits in high ghrelin states.
胃饥饿素已知可调节食欲控制和细胞代谢。促肾上腺皮质释放因子 (CRF) 家族也已知可调节能量平衡。在这项研究中，研究了 C2C12 细胞（一种小鼠成肌细胞系）中胃饥饿素和 CRF 家族之间的联系。
用胃饥饿素处理 C2C12 细胞，同时存在或不存在 CRF 受体拮抗剂，然后进行不同的代谢分析。
胃饥饿素增强了 C2C12 细胞的葡萄糖摄取，诱导 GLUT4 向细胞表面易位，并降低了 RBP4 的表达。CRF-R2 选择性拮抗剂抗 Sauvagine-30 阻断了胃饥饿素诱导的葡萄糖摄取，胃饥饿素上调了 CRF-R2 但不上调 CRF-R1 水平。此外，用胃饥饿素处理的 C2C12 细胞在响应 Ucn3（CRF-R2 特异性配体）时显示出 cAMP 和 pERK 的激活，但对 CRF 或 stressin（CRF-R1 特异性配体）没有反应。胃饥饿素还诱导了 UCP2 和 UCP3 的表达，这被抗 Sauvagine-30 阻断。胃饥饿素不会诱导 C2C12 细胞摄取脂肪酸或 ACC 表达。尽管 C2C12 细胞明显对胃饥饿素表现出反应，但在 C2C12 细胞中未检测到已知的胃饥饿素受体 GHSR1a。
结果表明，胃饥饿素在调节肌肉葡萄糖方面发挥作用，并提出抑制 CRF-R2 途径可能在高胃饥饿素状态下提供益处的可能性。
