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)

Galanin-like peptide (GALP) is a novel orexigenic neuropeptide that is recently isolated from the porcine hypothalamus. GALP-containing neurons predominantly locate in the hypothalamic arcuate nucleus (ARC). The expression of GALP mRNA within the ARC is increased after the administration of leptin. GALP-containing neurons express leptin receptor and contain alpha-melanocyte-stimulating hormone. We have recently reported that neuropeptide Y (NPY)- and orexin-containing axon terminals are in close apposition with GALP-containing neurons in the ARC. In addition, GALP-containing neurons express orexin-1 receptor (OX1-R). Thus, GALP may function under the influence of leptin and orexin. However, the target neurons of GALP have not yet been clarified. To clarify the neuronal interaction between GALP-containing and other feeding regulating neurons, double-immunostaining method using antibodies against GALP- and orexin- or melanin-concentrating hormone (MCH) was performed in the rat lateral hypothalamus (LH). GALP-immunoreactive fibers appeared to project to the LH around the fornix. They were also found from the rostral to the caudal part of the ARC, paraventricular nucleus (PVH), stria terminalis (BST), medial preoptic area (MPA), and lateral septal nucleus (LSV). Moreover, GALP-like immunoreactive nerve fibers were directly contacted with orexin- and melanin-concentrating hormone (MCH)-like immunoreactive neurons in the LH. Our findings strongly suggest that GALP-containing neurons interact with orexin- and/or MCH-containing neurons in the lateral hypothalamus and that it participates in the regulation of feeding behavior in harmony with other feeding-regulating neurons in the hypothalamus.
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PMID:Neuronal interactions between galanin-like-peptide- and orexin- or melanin-concentrating hormone-containing neurons. 1562 Apr 18

Both growth hormone (GH)/insulin growth factor (IGF)-1 axis and energy balance have been implicated in longevity independently. The aim of the present study was to characterize the effect of a 72-h fasting period at 3 months of age in four different rat strains: (i) Wistar and (ii) Fischer 344 rats, which develop obesity with age, and (iii) Brown Norway and (iv) Lou C rats, which do not. Wistar rats ate more, were significantly bigger, and presented with higher plasma leptin and lower ghrelin levels and hypothalamic growth hormone-releasing hormone (GHRH) content than rats from the three other strains. Plasma insulin and IGF-1 levels were lower in Brown Norway and Lou C rats, and somatostatin content was lower in Brown Norway rats only. Glycaemia was lower in Lou C rats that displayed a lower relative food intake compared to Fischer and Wistar rats. Brown Norway rats showed a greater caloric efficiency than the three other strains. Concerning major hypothalamic neuropeptides implicated in feeding, similar amounts were detected in the four strains for neuropeptide Y, agouti-related peptide, galanin, melanin-concentrating hormone, alpha-melanocortin-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone. Orexin A appeared to be slightly elevated in Fischer rats and cocaine amphetamine-regulated transcript (CART)(55-102) diminished in Brown Norway. At the mRNA level, orexin A, GHSR1, alpha-MSH and CART expression were higher in Wistar and Lou C rats. Principal component analysis confirmed the presence of two main factors in the ad libitum rat population; the first being associated with growth-related parameters and the second being associated with food intake regulation. Hypothalamic GHRH and somatostatin content were positively correlated with feeding-related neuropeptides such as alpha-MSH for GHRH, and orexin A and CART for both peptides. Plasma ghrelin levels were negatively correlated with leptin and IGF-1 levels. Finally, a 72-h fasting period affected minimally body weight, plasma IGF-1 and leptin levels in Lou C rats compared to the three other strains, and plasma insulin levels were less affected in Brown Norway rats. In conclusion, Wistar shorter life span is consistent with its already fatter phenotype at 3 months of age. In terms of IGF-1, glycaemia and leptin responses to fasting, the Lou strain, which presents with a low food intake/body weight and caloric efficiency, is the least affected. The link between food intake regulation, GH axis and ageing is further demonstrated by principal component analysis, where GHRH and somatostatin were found to be strongly associated with energy homeostasis parameters.
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PMID:Plasma and hypothalamic peptide-hormone levels regulating somatotroph function and energy balance in fed and fasted states: a comparative study in four strains of rats. 1566 53

The aim of this paper is to review the present knowledge on the role of the hypothalamic-pituitary-adrenal axis in the control of food intake and the pathogenesis of obesity and to discuss, on the basis of available literature, the interactions between other neurosystems and this hormonal axis. Food intake is influenced by a system of physiologic signals and behavioral controls consisting of positive and negative sensory feedback mechanisms. It is regulated by a complex neuroendocrine system consisting of peripheral signals (cortisol, leptin) in constant interplay with central neurosystems such as the cocaine-amfetamine-regulated transcript system. In these neurosystems, corticotropin-releasing hormone, pro-opiomelanocortin, melanin-concentrating hormone and neuropeptide Y are actively involved. The corticotropin-releasing hormone system is widely distributed throughout the brain, but it is particularly abundant in the medial parvocellular division of the paraventricular nucleus. Within the brain corticotropin-releasing hormone with its two receptor types, its binding protein and its closely related peptide urocortin forms a network of neuronal pathways capable of interacting with other circuitries controlling food intake and sympathetically-mediated thermogenesis. A defect in the synthesis and release of corticotropin-releasing hormone has been implicated in the development of obesity in laboratory animals. This condition is alleviated by exogenous corticotropin-releasing hormone treatment. The relationship between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis is complex and seems to include positive feedback between neuropeptide Y and corticosteroids and negative feedback between corticotropin-releasing hormone and neuropeptide Y. Leptin is involved in the regulation of energy balance by interacting with the hypothalamic-pituitary-adrenal axis. In the past, we have shown by cross-correlation analysis, that under physiological conditions cortisol and plasma leptin levels are related to each other in a time-related negative and positive fashion over 24h.
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PMID:The hypothalamic-pituitary-adrenal axis in the neuroendocrine regulation of food intake and obesity: the role of corticotropin releasing hormone. 1568 23

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a pituitary hormone derived by post-translational processing from proopiomelanocortin and is involved in background adaptation in teleost fish. It has also been reported to suppress food intake in mammals. Here, we examined the immunocytochemical localization of alpha-MSH in the brain and pituitary of a pleuronectiform fish, the barfin flounder (Verasper moseri), as a first step in unraveling the possible function of alpha-MSH in the brain. The ontogenic development of the alpha-MSH system was also studied. In the pituitary, alpha-MSH-immunoreactive (ir) cells were preferentially detected in the pars intermedia. In the brain, alpha-MSH-ir neuronal somata were located in the nucleus tuberis lateralis of the basal hypothalamus, and alpha-MSH-ir fibers were located mainly in the telencephalon, hypothalamus, and midbrain. Alpha-MSH-ir neuronal somata did not project their axons to the pituitary. The alpha-MSH-ir neurons differed from those immunoreactive to melanin-concentrating hormone. Alpha-MSH cells in the pituitary and alpha-MSH-ir neuronal somata in the brain were first detected 1 day and 5 days after hatching, respectively. The distribution of alpha-MSH-ir cells, neuronal somata, and fibers showed a pattern similar to that in adult fish 30 days after hatching. These results indicate that the functions of alpha-MSH in the brain and pituitary are different and that alpha-MSH plays physiological roles in the early development of the barfin flounder.
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PMID:Immunocytochemical localization and ontogenic development of alpha-melanocyte-stimulating hormone (alpha-MSH) in the brain of a pleuronectiform fish, barfin flounder. 1572 22

Melanocortins are known to be involved in the inhibition of food intake and energy metabolism. Acute and chronic intracerebroventricular administration of several different analogues of alpha-MSH, such as alpha-MSH, NDP-MSH, alpha-MSH-ND, [Gln(6)]alpha-MSH-ND, and [Lys(6)]alpha-MSH-ND, which were substituted in the position of His(6) with Gln and Lys, and cyclic16k-MSH to C57J/BL6 mice resulted in a significant inhibition of both time course food intake and body weight gain, compared to the saline-administered control. However, [Gln(6)]alpha-MSH-ND(6-10), the truncated form of [Gln(6)]alpha-MSH-ND, had no inhibitory effects on food intake. In situ hybridization analysis revealed that the expression levels of AGRP and NPY in the hypothalamus were significantly and rapidly diminished while POMC expression was strongly induced by [Gln(6)]alpha-MSH-ND. Administration of JKC-363, a selective MC4R-specific antagonist, coupled with [Gln(6)]alpha-MSH-ND, specifically reversed the [Gln(6)]alpha-MSH-ND-induced inhibition of food intake, but also reversed the hypothalamic expression levels of neuropeptides such as AGRP, NPY, MCH, and POMC, which suggests [Gln(6)]alpha-MSH-ND can function as a selective MC4R agonist.
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PMID:Dynamic regulation of hypothalamic neuropeptide gene expression and food intake by melanocortin analogues and reversal with melanocortin-4 receptor antagonist. 1576 51

Appetite regulation is part of a feedback system that controls the energy balance, involving a complex interplay of hunger and satiety signals, produced in the hypothalamus as well as in peripheral organs. Hunger signals may be generated in peripheral organs (e.g. ghrelin) but most of them are expressed in the hypothalamus (neuropeptide Y, orexins, agouti-related peptide, melanin concentrating hormone, endogenous opiates and dopamine) and are expressed during situations of energy deficiency. Some satiety signals, such as cholecystokinin, glucagon-like peptide 1, peptide YY and enterostatin are released from the digestive tract in response to food intake. Others, such as leptin and insulin, are mobilized in response to perturbations in the nutritional state. Still others are generated in neurones of the hypothalamus (alpha-melanocyte-stimulating hormone and serotonin). Satiety signals act by inhibiting the expression of hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in fat and sugar, up-regulates the expression of hunger signals and satiety signals, at the same time blunting the response to satiety signals and activating the reward system. Hence, palatable food offsets normal appetite regulation, which may explain the increasing problem of obesity worldwide.
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PMID:How palatable food disrupts appetite regulation. 1599 51

The neurochemistry of feeding was a highlight of this meeting. A number of peptides are now known to participate in the control of nutrient balance, and many of them featured in the meeting, including the feeding suppressors alpha-melanocyte-stimulating hormone, leptin and corticotrophin releasing hormone, and the orexigenic agents, melanin-concentrating hormone, Agouti-related peptide, orexin A and neuropeptide Y. Other substances that play a role in feeding are amylin and its antagonist, AC-187, histamine, dopamine, serotonin, opiates, galanin and CART peptides. The hypothalamic and extrahypothalamic localization of these feedingrelated substances and their interactions with one another, and other brain regions, are beginning to be understood. Another symposium focused on sigma receptor ligands, such as (+)-pentazocine, PRE-084, the neurosteroid pregnanolone sulfate, NE-100, igmesine (JO-1784) and BD-1008 and related compounds. Results showed that sigma ligands may affect Ca(2+) signaling via two modes of action, one being at the endoplasmic reticulum and the other at the plasma membrane. Sigma receptors have been implicated in learning and memory, and may play a role in anxiety and depression.
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PMID:International Behavioral Neuroscience Society - Ninth meeting. Neurochemistry of feeding. 1608 42

When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.
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PMID:Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats. 1621 17

A number of different neuropeptides exert powerful concerted controls on feeding behavior and energy balance, most of them being produced in hypothalamic neuronal networks under stimulation by anabolic and catabolic peripheral hormones such as ghrelin and leptin, respectively. These peptide-expressing neurons interconnect extensively to integrate the multiple opposing signals that mediate changes in energy expenditure. In the present review I have summarized our current knowledge about two key peptidic systems involved in regulating appetite and energy homeostasis, the melanocortin system (alpha-MSH, agouti and Agouti-related peptides, MC receptors and mahogany protein) and the melanin-concentrating hormone system (proMCH-derived peptides and MCH receptors) that contribute to satiety and feeding-initiation, respectively, with concurrent effects on energy expenditure. I have focused particularly on recent data concerning transgenic mice and the ongoing development of MC/MCH receptor antagonists/agonists that may represent promising drugs to treat human eating disorders on both sides of the energy balance (anorexia, obesity).
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PMID:The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis. 1686 Feb 80

The melanocortin system is an important treatment target towards improving both adiposity (excessive body fat) and adiposopathy (dysfunctional body fat). Melanocortin agonism can be achieved by increasing CNS leptin and/or insulin activity, which is dependent upon peripheral leptin/insulin production, transport across the blood-brain barrier (potentially relevant to inhaled/nasal insulin), and effects upon CNS target receptors. Melanocortin agonism may also be achieved through inhibiting inverse agonists of melanocortin receptors (such as inhibition of agouti-related peptide), and directly through selective melanocortin receptor ligands such as piperazine, piperidine, pyridazinone, tetrahydropyran, thiadiazole and diazole derivatives. While the development of most (but not all) neuropeptide Y inhibitors as monotherapy interventions have demonstrated limited efficacy thus far, it is possible that the combination of a neuropeptide Y inhibitor with a selective melanocortin receptor ligand may provide improved weight loss over that of either agent alone. In general, melanocortin system agonism promotes weight loss through decreasing appetite, increasing sympathetic nervous system activity, and modulating thyroid-releasing hormone, corticotropin-releasing hormone, brain-derived neurotrophic factor, melanin-concentrating hormone and orexin. Of particular interest, given the development of cannabinoid receptor antagonists as weight loss agents, is the fact that receptors in the endocannabinoid system are also affected by the melanocortin system. It will only be through the conduct of human clinical trials that melanocortin agonists will be proven to reduce adiposity to a meaningful degree, and, as importantly, be proven to improve adiposopathy, and thus effectively treat excessive fat-related metabolic diseases.
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PMID:The melanocortin system as a therapeutic treatment target for adiposity and adiposopathy. 1692 90


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