Ghrelin, A Novel Peptide Hormone in the Regulation of Energy Balance and Cardiovascular Function

Carola      Ledderose; Simone      Kreth; Andres      Beiras-Fernandez

doi:10.2174/187221411794351897

Abstract

Ghrelin, a peptide hormone predominantly produced by the stomach, is a potent stimulator of growth hormone release, food intake and weight gain. Besides its functions in regulating energy homeostasis, ghrelin has pronounced cardioprotective effects and was shown to improve cardiac performance in chronic heart failure (CHF). The multifunctional nature of ghrelin makes it an interesting pharmacological target for various diseases. Inhibition of ghrelin could be a promising approach in obesity-related disorders, while an enhancement of the ghrelin response is considered beneficial in several pathologic conditions marked by malnutrition, wasting and cachexia, including CHF, cancer, chronic pulmonary disease or chronic infections. In particular, patients suffering from CHF could possibly benefit from ghrelinbased compounds that do not only help to reverse cardiac cachexia - by inducing a positive energy balance - but also enhance the direct cardioprotective effects of ghrelin. This review highlights the role of ghrelin in the regulation of energy balance and cardiovascular function and summarizes the most recent patents, developments and strategies in ghrelin-based pharmacotherapy for the treatment of pathologic conditions associated with obesity, cachexia or cardiovascular dysfunction.

Keywords: Cachexia, chronic heart failure, energy metabolism, ghrelin, obesity, patents, dysfunctions, cardio-vascular, hypertension, cancer, hypercatabolic state, congestive, chronic kidney disease, chronic obstruc-tive, sepsis, homeostasis, peripheral organs, endogenous ligand, insulin, adipocytokines, ghrelin receptor, endothelial cells, binding affinities, des-acylated ghrelin, melanocortin receptors (MCR), proopiomelanocortin (POMC), mediators, anorexigenic signaling, carbohydrates, noradrenalin, possibly reflecting, hypercholesterinemia, orexigenic, drug development, stereochemistry, myocardial function, left ventri-cular, remodeling, pathophysiology, renin-angiotensin system, glucose metabolism, dyslipidemia, inflammatory states