Original Research ARTICLE

Front. Endocrinol., 02 November 2011 | http://dx.doi.org/10.3389/fendo.2011.00067

Ghrelin receptor deficiency does not affect diet-induced atherosclerosis in low-density lipoprotein receptor-null mice

Kirk M. Habegger1, Erin Grant1, Paul Thomas Pfluger1,2, Diego Perez-Tilve1, Alan Daugherty3, Dennis Bruemmer3, Matthias H. Tschöp1,2* and Susanna M. Hofmann1,4
  • 1 Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH, USA
  • 2 Institute for Diabetes and Obesity, German Research Center for Environmental Health, München/Neuherberg, Germany
  • 3 Saha Cardiovascular Research Center, University of Kentucky College of Medicine, Lexington, KY, USA
  • 4 Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München/Neuherberg, Germany

Objective: Ghrelin, a stomach-derived, secreted peptide, and its receptor (growth hormone secretagogue receptor, GHSR) are known to modulate food intake and energy homeostasis. The ghrelin system is also expressed broadly in cardiovascular tissues. Since ghrelin has been associated with anti-inflammatory and anti-atherogenic properties, but is also well known to promote obesity and impair glucose metabolism, we investigated whether ghrelin has any impact on the development of atherosclerosis. The hypothesis that endogenous ghrelin signaling may be involved in atherosclerosis has not been tested previously. Methods and Results: We crossed ghrelin receptor knockout mice (GHSr−/−) into a low-density lipoprotein receptor-null (Ldlr−/−) mouse line. In this model, atherosclerotic lesions were promoted by feeding a high-fat, high-cholesterol Western-type diet for 13 months, following a standard protocol. Body composition and glucose homeostasis were similar between Ldlr−/− and Ldlr/GHSR−/−ko mice throughout the study. Absence or presence of GHSr did not alter the apolipoprotein profile changes in response to diet exposure on an LDLRko background. Atherosclerotic plaque volume in the aortic arch and thoracic aorta were also not affected differentially in mice without ghrelin signaling due to GHSR gene disruption as compared to control LDLRko littermates. In light of the associations reported for ghrelin with cardiovascular disease in humans, the lack of a phenotype in these loss-of-function studies in mice suggests no direct role for endogenous ghrelin in either the inhibition or the promotion of diet-induced atherosclerosis. Conclusion: These data indicate that, surprisingly, the complex and multifaceted actions of endogenous ghrelin receptor mediated signaling on the cardiovascular system have minimal direct impact on atherosclerotic plaque progression as based on a loss-of-function mouse model of the disease.

Keywords: ghrelin, LDL receptor, atherosclerosis

Citation: Habegger KM, Grant E, Pfluger PT, Perez-Tilve D, Daugherty A, Bruemmer D, Tschöp MH and Hofmann SM (2011) Ghrelin receptor deficiency does not affect diet-induced atherosclerosis in low-density lipoprotein receptor-null mice. Front. Endocrin. 2:67. doi: 10.3389/fendo.2011.00067

Received: 13 September 2011; Paper pending published: 24 September 2011;
Accepted: 15 October 2011; Published online: 02 November 2011.

Edited by:

Francisco Gracia-Navarro, University of Cordoba, Spain

Reviewed by:

Rhonda D. Kineman, University of Illinois at Chicago, USA
Raul Miguel Luque Huertas, University of Cordoba, Spain
Sabrina Diano, Yale University School of Medicine, USA

Copyright: © 2011 Habegger, Grant, Pfluger, Perez-Tilve, Daugherty, Bruemmer, Tschöp and Hofmann. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Matthias H. Tschöp, Division of Endocrinology, Department of Medicine, Metabolic Disease Institute, University of Cincinnati College of Medicine, 2170 E Galbraith Road, Cincinnati, OH 45237, USA. e-mail: tschoemh@ucmail.uc.edu