CRF type 2 receptors mediate the metabolic effects of ghrelin in C2C12 cells


  • Funding agencies: This work was supported by grants from the Foundation for Prader-Willi Research and The Machiah Foundation, a supporting foundation of the Jewish Community Federation and Endowment Fund and in part by the Clayton Medical Research Foundation, Inc. and the National Institute of Diabetes and Digestive and Kidney Diseases Program Project Grant DK 026741-33. The project described was supported by Award Number DK026741 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

  • Disclosure: The authors declared no conflict of interest.

  • Author contributions: WWV conceived experiments. All authors were involved in writing the paper and had final approval of the submitted and published versions.



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.

Design and Methods

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.