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

• Published in: Obesity (Silver Spring, Md.) Vol. 22; no. 2; pp. 380 - 389
• Main Authors: Gershon, Eran, Vale, Wylie W.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2014
• Subjects: Animals; Antibodies, Blocking - pharmacology; Binding sites; Biological Transport - drug effects; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Fatty acids; Gene Expression Regulation - drug effects; Ghrelin - metabolism; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Growth hormones; Ion Channels - agonists; Ion Channels - genetics; Ion Channels - metabolism; Metabolism; Mice; Mitochondrial Proteins - agonists; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Musculoskeletal system; Myoblasts - drug effects; Myoblasts - metabolism; Myoblasts - ultrastructure; Protein Transport - drug effects; Pyrimidines - pharmacology; Pyrroles - pharmacology; Receptors, Corticotropin-Releasing Hormone - agonists; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Corticotropin-Releasing Hormone - metabolism; Receptors, Ghrelin - genetics; Receptors, Ghrelin - metabolism; Retinol-Binding Proteins, Plasma - antagonists & inhibitors; Retinol-Binding Proteins, Plasma - genetics; Retinol-Binding Proteins, Plasma - metabolism; Rodents; Signal Transduction - drug effects; Studies; Uncoupling Protein 2; Uncoupling Protein 3; Urocortins - metabolism; Weight control
• ISSN: 1930-7381; 1930-739X; 1930-739X
• DOI: 10.1002/oby.20535

Objective 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. Results 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. Conclusion 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.