Ghrelin as a Potential Anti-Obesity Target

Tamas   L.   Horvath; Tamara      Castaneda; Mads      Tang-Christensen; Uberto      Pagotto; Matthias   H.   Tschop

doi:10.2174/1381612033454748

Abstract

In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appears to be the only potent hungerinducing factor to naturally circulate in our blood stream, was discovered in 1999. Since then the acylated peptide hormone ghrelin has evolved from an endogenous growth hormone secretagogue to a regulator of energy balance to a pleiotropic hormone with multiple sources, numerous target tissues and most likely several physiological functions. Although neither the exact mechanism of action by which ghrelin increases food intake and adiposity is known, nor the putatively differential effects of brain-derived and stomach-derived ghrelin on energy homeostasis have been determined, blocking or neutralizing ghrelin action still seems one of the more reasonable pharmacological approaches to reverse a chronically positive energy balance. However, based on growing experience with compounds targeting the neuroendocrine regulation of energy balance, it is quite possible that a ghrelin antagonist will either fail to cure obesity due to the existence of compensatory mechanisms or undesired effects might reveal the true biological function of ghrelin (e.g. cardiovascular mechanisms, anti-proliferative effects, reproduction).

Keywords: ghrelin, anti-obesity target, gastric endocrine agent, acylated peptide hormone

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