Obestatin is a recently discovered 23 amino acids peptide derived from the ghrelin gene. As opposed to ghrelin, obestatin was shown to inhibit food intake in mice. The aims of this research were to study the effects of acute obestatin treatment on feeding behavior in the rat and its effects on GH and corticosterone secretion. Our results demonstrate that in young-adult male rats, obestatin effectively blunts the hunger caused by short-term starvation. Obestatin did not modify GH secretion in 10-day-old rats and did not antagonize the GH-releasing effects of hexarelin. Moreover, obestatin administration had no effects on spontaneous corticosterone secretion. In conclusion, these data demonstrate that in young-adult male rats the newly discovered obestatin can inhibit feeding but does not modify GH and corticosterone release in infant rats.

Data from Alzheimer's disease (AD) patients and AD animal models demonstrate the accumulation of inflammatory microglia at sites of insoluble fibrillar beta-amyloid protein (fAbeta) deposition. It is known that fAbeta binds to CD36, a type B scavenger receptor also involved in internalization of oxidized low-density lipoprotein (LDL), and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death. The recent demonstration of a binding site for the growth hormone secretagogues (GHS) on CD36 prompted us to ascertain whether ghrelin and synthetic GHS could modulate the synthesis of inflammatory cytokines in fAbeta-activated microglia cells. We demonstrate that N9 microglia cells express the CD36 and are a suitable model to study the activation of inflammatory cytokines synthesis. In fact, in N9 cells exposed to fAbeta(25-35) for 24 hr, the expression of interleukin (IL)-1beta and IL-6 mRNA significantly increased. Interestingly, 10(-7) M desacyl-ghrelin, hexarelin, and EP80317 in the nanomolar range effectively counteracted fAbeta(25-35) stimulation of IL-6 mRNA levels, whereas ghrelin was ineffective. Similarly, the effects of fAbeta(25-35) on IL-1beta mRNA levels were attenuated by desacyl-ghrelin, hexarelin, and EP80317, but not ghrelin. Because we have observed that the specific GHS receptor GHS-R1a is not expressed in N9 cells, the actions of GHS should be mediated by different receptors. Reportedly, hexarelin and EP80317 are capable of binding the CD36 in mouse macrophages and reducing atherosclerotic plaque deposition in mice. We conclude that desacyl-ghrelin, hexarelin, and EP80317 might interfere with fAbeta activation of CD36 in microglia cells.

The hypothalamic-pituitary-adrenal (HPA) axis is a major integrated system that maintains body homeostasis by regulating the neuroendocrine and sympathetic nervous systems and modulating immune function. It is well established that the central nervous system (CNS) integrates responses to different stimuli secreting a specific corticotropin-releasing hormone (CRH) and vasopressin (AVP). In turn, they stimulate the release of ACTH, which induces steroidogenesis in the adrenal gland. The HPA axis is regulated by diurnal rhythms and negative feedback by corticosteroids. Many neurotransmitters and neuropeptides are responsible for the modulation of CRH and AVP neurons. In addition to synthetic glucocorticoids that inhibit the HPA axis, GABA agonists, opioid peptides and endocannabinoids can inhibit cortisol secretion. On the contrary, serotonin, norepinephrine, dopamine, acetylcholine, ghrelin, angiotensin II and different cytokines can stimulate it. It follows that a number of neuroactive drugs, acting as agonists or antagonists on several brain neurotransmitter or neuropeptide receptors, can influence ACTH/cortisol secretion thereby interfering with clinical testing of the functionality of the HPA axis.

Recently, we demonstrated that TLQP-21 triggers lipolysis and induces resistance to obesity by reducing fat accumulation [1]. TLQP-21 is a 21 amino acid peptide cleavage product of the neuroprotein VGF and was first identified in rat brain. Although TLQP-21 biological activity and its molecular signaling is under active investigation, a receptor for TLQP-21 has not yet been characterized. We now demonstrate that TLQP-21 stimulates intracellular calcium mobilization in CHO cells. Furthermore, using Atomic Force Microscopy (AFM), we also provide evidence of TLQP-21 binding-site characteristics in CHO cells. AFM was used in force mapping mode equipped with a cantilever suitably functionalized with TLQP-21. Attraction of this functionalized probe to the cell surface was specific and consistent with the biological activity of TLQP-21; by contrast, there was no attraction of a probe functionalized with biologically inactive analogues. We detected interaction of the peptide with the binding-site by scanning the cell surface with the cantilever tip. The attractive force between TLQP-21 and its binding site was measured, statistically analyzed and quantified at approximately 40 pN on average, indicating a single class of binding sites. Furthermore we observed that the distribution of these binding sites on the surface was relatively uniform.

No abstract