OBESTATIN · OBESTATIN AS A REGULATOR OF ENERGY BALANCE: NEUROENDOCRINE TARGETS AND MOLECULAR MECHANISMS

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Project objective

Ghrelin is a 28aamino acid peptide derived from a prepropeptide of 117 residues, named pre-proghrelin. Very recently it was identified a new ghrelin-associated peptide encoded by a 23aamino acid peptide, with a flanking conserved glycine residue at the C terminus named obestatin. Obestatin showed a high affinity for GPR39 and needs an amidation to be biologically active. Regarding its physiological effects, obestatin is able to antagonize ghrelin effects on food intake, body weight and gastric emptying, but had no effect on growth hormone levels. Intraperitoneal and intracerebroventricular injection of obestatin suppressed food intake in a time- and dose-dependent manner. In contrast, treatment with the non-amidated obestatin was less effective. The fact that the same precursor leads to two different peptides with orexigenic and anorexigenic actions shows us that energy balance depends not only of the expression of different peptides but also the rate of transcription from the precursor to aSleana or aSfata gene is very important. As it is typical when a new discovery appears, numerous unanswered questions arise and further studies will be necessary to find those answers. For instance, even obestatin decreased the food intake and body weight in rodents, serum leptin levels were not affected after treatment with obestatin, suggesting minimal modulation of body-fat content. Moreover, fasting did not change serum obestatin levels and circulating levels of obestatin are much lower than ghrelin, thus the relevance of endogenous obestatin remains unclear. Finally, from a pharmacological point of view, the most interesting will be to check if obestatin changes the food intake or the body weight in humans.

Original text from CORDIS.

Participants

• UNIVERSIDADE DE SANTIAGO DE COMPOSTELA · SANTIAGO DE COMPOSTELACoordinatorSpain
• UNIVERSITY OF CINCINNATI OBESITY RESEARCH CENTRE · CINCINNATICity levelUnited States

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