Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide alpha-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.
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PMID:Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. 1803 82

In goldfish, intracerebroventricular (ICV) administration of melanin-concentrating hormone (MCH) inhibits feeding behavior, and fasting decreases hypothalamic MCH-like immunoreactivity. However, while MCH acts as an anorexigenic factor in goldfish, in rodents MCH has an orexigenic effect. Therefore, we examined the involvement of two anorexigenic neuropeptides, alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone (CRH), in the anorexigenic action of MCH in goldfish, using an alpha-MSH receptor antagonist, HS024, and a CRH receptor antagonist, alpha-helical CRH((9-41)). ICV injection of HS024, but not alpha-helical CRH((9-41)), suppressed MCH-induced anorexigenic action for a 60-min observation period. We then examined, using a real-time PCR method, whether MCH affects the levels of mRNAs encoding various orexigenic neuropeptides, including neuropeptide Y (NPY), orexin, ghrelin and Agouti-related peptide (AgRP), in the goldfish diencephalon. ICV administration of MCH at a dose sufficient to inhibit food consumption decreased the expression of mRNAs for NPY and ghrelin, but not for orexin and AgRP. These results indicate that the anorexigenic action of MCH in the goldfish brain is mediated by the alpha-MSH signaling pathway and is accompanied by inhibition of NPY and ghrelin synthesis.
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PMID:Alpha-melanocyte-stimulating hormone mediates melanin-concentrating hormone-induced anorexigenic action in goldfish. 1805 11

Bilateral lesions of the hypothalamic paraventricular nuclei (PVN) induce hyperphagia and obesity, and ghrelin stimulates appetite in rodents and humans. Conversely, corticotrophin-releasing hormone (CRH) and melanotan-II (MT-II, a synthetic structural homologue of alpha-melanocyte-stimulating hormone, alphaMSH) inhibit feeding behavior. The purpose of the present study was to determine whether these peptides are involved in the hyperphagia and obesity induced by PVN lesions. After bilateral electrolytic lesions of the PVN, rats were given ghrelin intraperitoneally (i. p.), or intracerebroventricular (i. c. v.) infusion of CRH or MT-II. We measured the cumulative food intake (FI) for 4 h after ghrelin injection in rats fed AD LIB, and the changes in FI at 15 min, 30 min, 1 h, and 2 h after infusion of CRH and MT-II in rats fasted for 24 h. Ghrelin significantly increased cumulative FI, with maximal response 3 h and 4 h after injection, and at these times, the FI of PVN-lesioned rats was greater than that of sham-operated rats. CRH significantly decreased FI in all experimental animals, but at 1 h, there was a more powerful inhibitory effect on FI in the PVN-lesioned group than in the sham-operated group. MT-II decreased FI in sham-operated, but not in PVN-lesioned rats. Thus, ghrelin and CRH showed more potent orexigenic and anorectic effects in PVN-lesioned rats, respectively, but MT-II lost its inhibitory action on feeding behavior. These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin due to the destruction of endogenous CRH and alphaMSH receptors.
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PMID:Effects of ghrelin, corticotrophin-releasing hormone, and melanotan-II on food intake in rats with paraventricular nucleus lesions. 1805 2

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.
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PMID:Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations. 1822 38

Nitric oxide (NO) is known as an orexigenic factor in the brain of mammals and mediates the feeding-stimulatory effect of other factors such as neuropeptide Y (NPY). In neonatal chicks, however, we recently reported that NO might have an anorexigenic effect and suggested that the feeding-regulatory mechanism in chicks might be different from that in mammals regarding NO. In the present study, we investigated the involvement of NO in the effect of other orexigenic and anorexigenic factors in neonatal chicks. Intracerebroventricular co-injection of N(G)-nitro-l-arginine methyl ester (l-NAME), a NO synthase inhibitor, did not affect NPY- and prolactin-releasing peptide-induced feeding behavior. On the other hand, the co-injection of l-NAME significantly attenuated the anorexigenic effect of corticotropin-releasing hormone (CRH). The anorexigenic effects of glucagon-like peptide-1, alpha-melanocyte-stimulating hormone and ghrelin were not affected by the l-NAME treatment. These results suggest that NO might mediate the anorexigenic effect of CRH in the brain of neonatal chicks.
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PMID:Nitric oxide synthase inhibitor attenuates the anorexigenic effect of corticotropin-releasing hormone in neonatal chicks. 1828 Jul 62

Ghrelin activates the somatotropic and the hypothalamic-pituitary-adrenal axes, being crucially involved in sleep regulation. Simplified, growth hormone releasing hormone (GHRH) increases slow-wave sleep and REM sleep in males, whilst corticotropin-releasing hormone (CRH) increases wakefulness and decreases REM sleep. Ghrelin's role in sleep regulation and particularly its interactions with GHRH and CRH are not entirely clear. We aimed to elucidate the interactions between ghrelin, GHRH and CRH in sleep regulation and the secretion of cortisol and GH. Nocturnal GH and cortisol secretion and polysomnographies were determined in 10 healthy males (25.7+/-3.0 years) four times, receiving placebo (A), ghrelin (B), ghrelin and GHRH (C), or ghrelin and CRH (D) at 22:00, 23:00, 00:00, and 01:00h, in this single-blind, randomized, cross-over study. Non-REM sleep was significantly (p<0.05) increased in all verum conditions (mean+/-SEM: B: 355.3+/-7.4; C: 365.4+/-8.1; D: 371.4+/-3.9min) compared to placebo (336.3+/-6.8min). REM sleep was decreased (B: 84.3+/-4.2 [p<0.1]; C: 74.2+/-7.0 [p<0.05]; D: 80.4+/-2.7min [p<0.05]) compared to placebo (100.9+/-8.3). CRH+ghrelin decreased the time spent awake and enhanced the sleep efficiency; furthermore, the REM latency was decreased compared to the other treatment conditions. CRH enhanced the ghrelin-induced cortisol secretion but had no relevant effect on GH secretion. In turn, GHRH enhanced the ghrelin-induced GH secretion but had no effect on cortisol secretion. In conclusion, ghrelin exhibited distinct sleep effects, which tended to be enhanced by both GHRH and CRH. CRH had sleep-improving and REM permissive effects when co-administered with ghrelin, being in contrast to the effect of CRH alone in previous studies.
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PMID:Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males. 1832 18

The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.
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PMID:UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. 1866 43

Novel neuropeptides acting as G-protein-coupled receptor (GPCR) ligands are known to be localized in the brain and play a range of physiologic functions, one of which is feeding regulation. We describe the distribution and localization of these recently identified GPCR ligands and review their involvement in neuronal networks, particularly in feeding regulation. This review addresses aspects of some novel GPCR ligands, including feeding-regulating neuropeptides such as orexin, ghrelin, and galanin-like peptide and other known neuropeptides such as neuropeptide Y and pro-opiomelanocortin. These neuropeptides have been studied by our research group and others, particularly with regard to interactions in the hypothalamus of neurons containing these neuropeptides. In the hypothalamus, cross-talk among such neurons plays a key role in determining feeding states and feeding behavior. We describe some structural and functional characteristics of these neuropeptides and summarize the known interactions between the different kinds of feeding-regulating neurons and leptin-targeting neurons in the hypothalamus. Moreover, we present a new strategy for analyzing neural circuits involving these feeding-regulating GPCR ligands in the brain, with research in this field aided by the use of transgenic mouse models. We also present our recent results that involve aspects of feeding regulation, energy homeostasis, and body temperature regulation. Research in this field will serve the important role of clarifying neurologically based causes for appetite dysfunctions and diseases and may help in establishing new therapies for patients with such conditions.
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PMID:Neural networks of several novel neuropeptides involved in feeding regulation. 1872 82

The endocannabinoid system (ECS) consists of two receptors (CB(1) and CB(2)), several endogenous ligands (primarily anandamide and 2-AG), and over a dozen ligand-metabolizing enzymes. The ECS has deep phylogenetic roots and regulates many aspects of embryological development and homeostasis, including neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding, and metabolism. The ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic pathways) and peripherally (in adipocytes and pancreatic islet cells), acting through numerous anorexigenic and orexigenic pathways (e.g., ghrelin, leptin, orexin, adiponectin, endogenous opioids, and corticotropin-releasing hormone). Obesity leads to excessive endocannabinoid production by adipocytes, which drives CB(1) in a feed-forward dysfunction. Phylogenetic research suggests the genes for endocannabinoid enzymes, especially DAGLalpha and NAPE-PLD, may harbor mildly deleterious alleles that express disease-related phenotypes. Several CB(1) inverse agonists have been developed for the treatment of obesity, including rimonabant, taranabant, and surinabant. These drugs are efficacious at reducing food intake as well as abdominal adiposity and cardiometabolic risk factors. However, given the myriad beneficial roles of the ECS, it should be no surprise that systemic CB(1) blockade induces various adverse effects. Alternatives to systemic blockade include CB(1) partial agonists, pleiotropic drugs, peripherally restricted antagonists, allosteric antagonists, and endocannabinoid ligand modulation. The ECS offers several discrete targets for the management of obesity and its associated cardiometabolic sequelae.
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PMID:Critical role of the endocannabinoid system in the regulation of food intake and energy metabolism, with phylogenetic, developmental, and pathophysiological implications. 1878 18

Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.
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PMID:Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress. 1880 Mar 8


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