Ghrelin as a potential anti-obesity target.
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 hunger-inducing 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).
Horvath
Tamas L
TL
Dept. of Ob/Gyn, Yale University School of Medicine, New Haven, CT, USA.
Castañeda
Tamara
T
Tang-Christensen
Mads
M
Pagotto
Uberto
U
Tschöp
Matthias H
MH
D000273:Adipose Tissue / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008969:Molecular Sequence Data; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D036361:Peptide Hormones / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin
D019440:Anti-Obesity Agents; D054439:Ghrelin; D036361:Peptide Hormones; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin