UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion. Peripheral regulation includes satiety signals and adiposity signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal (GI) tract during a meal and, through the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC), where satiety signals are integrated with adiposity signals, namely leptin and insulin, and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits which finally elaborate the individual response to a meal. As for the neuropeptidergic system, ARC neurons secrete orexigenic substances, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Other brain areas involved in the control of food intake are located downstream the ARC: among these, the paraventricular nucleus (PVN), which produces anorexigenic peptides such as thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH). A great interest in endocannabinoids, important players in the regulation of food intake, has recently developed. In conclusion, the present work reviews the most recent insights into the complex and redundant molecular mechanisms regulating food intake, focusing on the most encouraging perspectives for the treatment of obesity.
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PMID:Neuroendocrine control of food intake. 1806 14

Considerable evidence suggests that dynorphin participates in the regulation of energy balance. In this study, we have used immunohistochemistry to investigate in detail the cellular localization of pro-dynorphin (DYN) immunoreactive cell bodies in the mediobasal hypothalamus with special reference to neurons producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, DYN immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc). Double-labeling revealed that DYN immunoreactivity was present in approximately 30% of pro-opiomelanocortin (POMC) neurons in the ventrolateral Arc as shown by presence of alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART). In contrast, DYN immunoreactivity was not demonstrated in agouti-related peptide (AgRP)- or neuropeptide Y (NPY) -containing neurons in the ventromedial aspect of the Arc. Dynorphin immunoreactivity was also colocalized with the vesicular acetylcholine (ACh) transporter (VAChT; a marker for cholinergic neurons) in the cell soma of Arc POMC neurons. Brainstem POMC neurons in the commissural part of the solitary tract nucleus (NTS) were devoid of DYN immunoreactivity, whereas DYN immunoreactivity was detected in a few NPY-containing NTS neurons and cholinergic DMX neurons. Our results showing presence of DYN together with alpha-MSH in a subpopulation of hypothalamic POMC neurons further point to the neurochemical heterogeneity of hypothalamic POMC neurons. The results suggest a role for DYN in control of energy balance by mediating the effect of peripheral hormones such as leptin and insulin.
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PMID:Dynorphin in pro-opiomelanocortin neurons of the hypothalamic arcuate nucleus. 1847 30

Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles (Lasiopodomys brandtii), both circulating leptin levels and food intake are elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food intake. Diminished hypothalamic leptin receptors and impaired leptin signal transduction are characteristic of central leptin resistance. The present study aimed to determine whether these characteristic modulations of leptin sensitivity occurred in pregnant Brandt's voles. The mRNA expression of the long form of the leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3), neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to controls, there was no significant change in hypothalamic Ob-Rb mRNA during the pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no differences were found in the mRNA expression of NPY, AgRP and CART in pregnant voles compared to controls. The elevation of SOCS3 mRNA together with disrupted leptin regulation of neuropeptides in the hypothalamus suggests that leptin resistance may develop in pregnant Brandt's voles.
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PMID:Hypothalamic suppressor-of-cytokine-signalling 3 mRNA is elevated and pro-opiomelanocortin mRNA is reduced during pregnancy in Brandt's voles (Lasiopodomys brandtii ). 1863 26

The protein fragment nesfatin-1 was recently implicated in the control of food intake. Central administration of this fragment results in anorexia and reduced body weight gain, whereas antisense or immunological nesfatin-1 antagonism causes increased food intake and overweight. Nesfatin-1 is derived from the precursor nucleobindin-2 (NUCB2). To identify the neurocircuitry underpinning the catabolic effects of NUCB2/nesfatin-1, we have used in situ hybridization and immunohistochemistry to map the distribution of this protein and its mRNA in the rat CNS and performed double-labeling experiments to localize its expression to functionally defined neuronal populations. These experiments confirm previous observations but also present several novel NUCB2 cell populations. Both NUCB2 mRNA and nesfatin-like immunoreactivity was most concentrated in the hypothalamus, in the supraoptic, paraventricular, periventricular and arcuate nuclei and the lateral hypothalamic area/perifornical region. Additionally, outside of the hypothalamus, labeling was observed in the thalamic parafascicular nucleus, the Edinger-Westphal nucleus, locus coeruleus, ventral raphe system, nucleus of solitary tract and in the preganglionic sympathetic intermediolateral cell column of the spinal cord, and the pituitary anterior and intermediate lobes. In neurons, immunoreactivity was almost exclusively confined to perikarya and primary dendrites with virtually no labeling of axonal terminals. Double-labeling immunohistochemistry revealed colocalization of nesfatin with vasopressin and oxytocin in magnocellular neuroendocrine neurons, thyrotropin-releasing hormone, corticotropin-releasing hormone, somatostatin, neurotensin, and growth-hormone-releasing hormone in parvocellular neuroendocrine neurons, pro-opiomelanocortin (but not neuropeptide Y) in the arcuate nucleus and melanin-concentrating hormone (but not hypocretin) in the lateral hypothalamus. Furthermore, nesfatin was extensively colocalized with cocaine- and amphetamine-regulated transcript in almost all NUCB2-expressing brain regions. These data reveal a wider distribution of NUCB2/nesfatin-1 than previously known, suggesting that the metabolic actions of this protein may involve not only feeding behavior but also endocrine and autonomic effects on energy expenditure. In addition, the subcellular distribution of nesfatin-like immunoreactivity indicates that this protein may not be processed like a conventional secreted neuromodulator.
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PMID:Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. 1876 Oct 59

Epidemiological studies show a link between low birthweight and increased obesity. In contrast, slow growth during the lactation period reduces obesity risk. The present study investigates the potential underlying mechanisms of these observations. Rats were established as follows: (i) control animals [offspring of control dams fed a 20% (w/v) protein diet], (ii) recuperated animals [offspring of dams fed an isocaloric low-protein (8%, w/v) diet during pregnancy and nursed by control dams], and (iii) postnatal low protein animals (offspring of control dams nursed by low-protein-fed dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridization. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (P<0.05). At 21 days, they were hypoleptinaemic compared with controls in the fed state, with generally comparable hypothalamic gene expression. Postnatal low protein offspring had significantly lower body weights than controls at weaning and 12 weeks of age (P<0.001). At 21 days, they were hypoglycaemic, hypoinsulinaemic and hypoleptinaemic. Leptin receptor gene expression in the arcuate nucleus was increased in postnatal low protein animals compared with controls. Consistent with hypoleptinaemia, hypothalamic gene expression for the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (Agouti-related peptide) was increased, and that for the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript) was decreased. These results suggest that the early nutritional environment can affect the development of energy balance circuits and consequently obesity risk.
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PMID:Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation. 1915 6

Hypothalamus is crucial in the control of energy intake and expenditure in mammals, presenting two interconnected populations of neurons producing orexigenic NPY/AgRP (neuropeptide Y; agouti related peptide) and anorexigenic POMC/CART (pro-opiomelanocortin; cocaine and amphetamine regulated transcript) neuropeptides. We aimed to shed more light on the response and sensitivity in the production of these neuropeptides to face nutritional changes, particularly food deprivation, and on the signals that regulate them. Male Wistar rats were fasted for 0, 4, 8 and 24h and refed for 3h after 8h fasting. mRNA levels of gastric and adipose tissue (retroperitoneal, mesenteric and inguinal) leptin, and of hypothalamic NPY, AgRP, POMC, CART, leptin receptor, SOCS3 (suppressor of cytokine signaling 3) and insulin receptor were analyzed. Gastric and circulating leptin, and circulating insulin, glucose and ghrelin were also determined. The only neuropeptide mRNAs that responded (increasing) to the short-term periods of fasting used were those of NPY (transiently) and AgRP, and these changes were accompanied by an increase in leptin receptor mRNA levels and by a decrease in adipose and gastric leptin expression and in the circulating levels of leptin, insulin and glucose, but without changes in circulating ghrelin. The elevation in AgRP and leptin receptor mRNA levels and the drop in circulating leptin were not reverted with refeeding. It is suggested that the induction of expression of the orexigenic molecules in NPY/AgRP neurons is an early event upon fasting, related with changes in leptin, insulin and glucose levels, but with the role of leptin signaling in particular.
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PMID:Induction of NPY/AgRP orexigenic peptide expression in rat hypothalamus is an early event in fasting: relationship with circulating leptin, insulin and glucose. 1925 6

Nociceptin/orphanin FQ (N/OFQ) was identified in 1995 as the endogenous ligand for the orphan G(i)/G(o)-coupled opioid receptor-like 1 receptor (NOP(1)). Exogenous N/OFQ increases food intake in mammals, but its effect and mode of action in chicks are not fully known. We report herein that N/OFQ (5.0 nmol) has a stimulatory effect on food intake in layer-type chicks over a 2-h period after intracerebroventricular (icv) injection. Thirty minutes after central injection of N/OFQ (5.0 nmol) the concentration of agouti-related protein (AGRP) mRNA in the diencephalon increased, while cocaine- and amphetamine-regulated transcript (CART) mRNA decreased. However, concentrations of neuropeptide Y, proopiomelanocortin and glutamate decarboxylase mRNAs, and of catecholamines and excitatory amino acids were not affected. Simultaneous administration of alpha-melanocyte stimulating hormone (alpha-MSH: 1.0 pmol), a competitor of AGRP, completely blocked the orexigenic effect of N/OFQ (5.0 nmol). These data suggest that N/OFQ functions in layer chicks as an orexigenic peptide in the central nervous system, and that the AGRP and the CART neurons may mediate this function, as in mammals.
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PMID:Effect of nociceptin/orphanin FQ on feeding behavior and hypothalamic neuropeptide expression in layer-type chicks. 1931 6

Numerous studies have demonstrated that administration of rimonabant (SR 141716), a CB(1) receptor antagonist, causes a decrease in energy intake. However, the mechanisms by which rimonabant exerts its anorectic actions are unclear. The main focus of the study reported here was to establish the chemical identity of neurons that may subserve the anorectic effects of rimonabant. As such three approaches were utilised: (i) the identification of rimonabant-activated neurons using Fos as a marker of neuronal activity; (ii) the identification of the chemical phenotype of rimonabant-activated neurons by combining immunocytochemical identification of Fos and feeding-related peptides; and (iii) the evaluation of the effect of rimonabant on messenger RNA (mRNA) and protein for a number of feeding-related peptides. Rimonabant-induced Fos-positive nuclei were localized within a range of discrete hypothalamic regions with a predominance in the parvocellular part of the paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus, arcuate nucleus and lateral hypothalamic area. Furthermore, Fos labelling within these hypothalamic regions was colocalized with anorexigenic and orexigenic peptides including melanin-concentrating hormone (MCH), orexin, cocaine- and amphetamine-regulated transcript (CART) and alpha-melanocyte-stimulating hormone (alpha-MSH). Rimonabant specifically induced a decrease in NPY and an increase in CART and alpha-MSH mRNA and protein, consistent with its effect in reducing food intake and increasing energy expenditure. As such these data provide insights into the mechanisms of action that may underpin rimonabant's effects on energy balance and body weight.
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PMID:Involvement of hypothalamic peptides in the anorectic action of the CB receptor antagonist rimonabant (SR 141716). 1949 94

Weight regain after weight loss is a major hurdle for combating obesity. The aim of this study is to examine orexigenic and anorectic neuropeptides of the hypothalamic arcuate nucleus (Arc) in response to weight loss after chronic energy intake restriction. Thirty mice were fed with a high-fat diet for 8 weeks and then classified as diet-induced obese (DIO; n=10) or diet-resistant (DR; n=10) mice according to the highest and lowest body weight gainers. Five mice from DIO and DR groups were placed on an energy restricted diet or continued on their high-fat diet ad libitum for 6 weeks. An additional five mice were on a LF diet throughout the course of this study as controls. Results showed that a six-week energy restricted diet completely reversed the increased body weight, fat mass and leptin in the DIO mice to the levels of the LF and DR mice. Arc neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression in DIO mice after obesity reversal were significantly higher than DIO mice without obesity reversal (17%, 47%, both p<0.05), while the Arc pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA showed no difference. Both NPY and AgRP expression in DIO mice were negatively correlated with plasma leptin (R=-0.78, p<0.05; R=-0.72, p<0.05). In conclusion, while chronic energy restriction will lead to weight loss, it can up-regulate hypothalamic orexigenic peptides, which may be an important contributing factor to weight regain after a weight loss program from an energy restricted diet.
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PMID:Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP, but no alteration in POMC/CART, mRNA expression in diet-induced obese mice. 1961 32

Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide agonist of the opioid N/OFQ receptor, has been implicated in the regulation of energy balance. In the present study, we have used immunohistochemistry to investigate the cellular localisation and colocalisation of N/OFQ-immunoreactive cell bodies in hypothalamic regions containing neurones producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, N/OFQ immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA). Double-labelling revealed that N/OFQ was present in some neurones located in the ventrolateral part of the Arc producing pro-opiomelanocortin, as shown by the presence of the anorexigenic peptides alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript and, occasionally, in single neurones of the ventrolateral Arc producing orexigenic agouti-related peptide, but not neuropeptide Y. N/OFQ immunoreactivity was also demonstrated in a few tyrosine hydroxylase- or dynorphin (DYN)-containing neurones in the dorsomedial part of the Arc. In the parvocellular PVN, N/OFQ was demonstrated in some thyrotrophin-releasing hormone- or DYN-, but not corticotrophin-releasing hormone-containing neurones. Most N/OFQ-immunoreactive neurones in the LHA contained orexin- and DYN, but not melanin-concentrating hormone. The results obtained, demonstrating the presence of N/OFQ in some alpha-MSH- and in many orexin-containing neurones, suggest a functional relationship between these neuropeptides and N/OFQ in the control of feeding behaviour and body weight.
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PMID:Nociceptin/orphanin FQ peptide in hypothalamic neurones associated with the control of feeding behaviour. 2002 27

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