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The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the(More)
Current evidence suggests that hypothalamic fatty acid metabolism may play a role in regulating food intake; however, confirmation that it is a physiologically relevant regulatory system of feeding is still incomplete. Here, we use pharmacological and genetic approaches to demonstrate that the physiological orexigenic response to ghrelin involves specific(More)
Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK),(More)
Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its(More)
Glial cell line-derived neurotrophic factor (GDNF) is expressed in many neuronal and non-neuronal tissues during development as well as in adult animals. GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF. Thereafter this complex binds to and activates the tyrosine kinase(More)
Ghrelin is a novel 28-amino acid peptide identified as the endogenous ligand for the GH secretagogue receptor (GHS-R). Besides its hallmark central neuroendocrine effects in the control of GH secretion and food intake, an unexpected reproductive facet of ghrelin has recently emerged because expression of this molecule and its cognate receptor has been(More)
GH secretagogues are an expanding class of synthetic peptide and nonpeptide molecules that stimulate the pituitary gland to secrete GH through their own specific receptor, the GH-secretagogue receptor. The cloning of the receptor for these nonclassical GH releasing molecules, together with the more recent characterization of an endogenous ligand, named(More)
AIM/HYPOTHESIS Perinatal overfeeding predisposes humans and rats to obesity and diabetes in later life. One classical model for studying the effect of early feeding is manipulation of the size of rat litters. Rats growing up in small litters gain more weight than rats growing up in normal-sized litters. Interestingly, these obese rats maintain this(More)
Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1)/p53 and AMP-activated protein kinase (AMPK) pathways, which ultimately increase the expression of agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARC). However,(More)
Recently, it has been described the role of fatty acid ethanolamides in the control of feeding behavior. Oleoylethanolamide (OEA) is a member of this family of lipid mediators regulating feeding. OEA acts suppressing feeding behavior through, at least partially, a peripheral mechanism. However, the interaction between this acylethanolamide and other(More)