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

The discovery of leptin in 1994 has led to astonishing advances in understanding the regulation of energy balance in rodents and humans. The demonstration of leptin receptors in hypothalamic regions known to play critical roles in regulating energy intake and body weight has produced considerable excitement in the field. Most attention has focused on the central actions of leptin. The receptor is present in several populations of neurons that express specific appetite-regulating neuropeptides for which both expression and release are regulated by leptin. Recent advances show that central leptin action is not limited to influencing energy balance. Leptin regulates a broad variety of processes and behaviors, such as blood pressure, neuroendocrine axes, bone mass, and immune function. The cloning of leptin receptors also led to parallel studies examining their signaling capacities in mammalian cell lines. The long-form receptor regulates multiple intracellular signaling cascades, including the classic janus activating kinase-signal transducer and activator of transcription (JAK-STAT) pathway, consistent with belonging to the cytokine-receptor superfamily and the phosphoinositol-3 kinase and adenosine monophosphate kinase pathways. Progress has been made in understanding the role of individual signaling pathways in vivo and the mechanisms by which specific neuropeptides are regulated. Regulation of the pro-opiomelanocortin (pomc) and the thyrotropin-releasing hormone (trh) genes by leptin is particularly well understood. Novel players in negative regulation of central leptin receptor signaling have been identified and open the possibility that these may be important in the development of leptin resistance and obesity. While initial focus was on the central effects of leptin, important actions have been discovered in peripheral tissues. These include roles of leptin to directly regulate immune cells, pancreatic beta cells, adipocytes, and muscle cells. Recent elucidation of a new signaling pathway in skeletal muscle affecting fatty acid metabolism has implications for regulation of insulin sensitivity and glucose metabolism. Recent progress in understanding central and peripheral leptin receptor signaling provides potential new targets for anti-obesity and anti-diabetes drug development.
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PMID:Leptin signaling in the central nervous system and the periphery. 1474 8

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor and some GHSs exert different effects on sleep electroencephalogram (EEG) and sleep-related hormone secretion in humans. Similar to GH-releasing hormone (GHRH) ghrelin promotes slow-wave sleep in humans, whereas GH-releasing peptide-6 (GHRP-6) enhances stage 2 nonrapid-eye movement sleep (NREMS). As GHRP-6, hexarelin is a synthetic GHS. Hexarelin is superior to GHRH and GHRP-6 in stimulating GH release. The influence of hexarelin on sleep-endocrine activity and the immune system is unknown. We investigated simultaneously the sleep EEG and nocturnal profiles of GH, ACTH, cortisol, prolactin, leptin, tumor necrosis factor (TNF)-alpha, and soluble TNF-alpha receptors in seven young normal volunteers after repetitive administration of 4 x 50 microg hexarelin or placebo at 22.00, 23.00, 24.00 and 01.00 h. Following hexarelin, stage 4 sleep during the first half of the night, and EEG delta power during the total night decreased significantly. Significant increases of the concentrations of GH and prolactin during the total night, and of ACTH and of cortisol during the first half of the night were found. Leptin levels, TNF-alpha and soluble TNF receptors remained unchanged. We hypothesize that sleep is impaired after hexarelin since the GHRH/corticotropin-releasing hormone (CRH) ratio is changed in favour of CRH. There are no hints for an interaction of hexarelin and the immune system.
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PMID:Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. 1517

Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-loxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.
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PMID:Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. 1520 5

Glucosensing neurons in the hypothalamic arcuate nucleus (ARC) were studied using electrophysiological and immunocytochemical techniques in neonatal male Sprague-Dawley rats. We identified glucose-excited and -inhibited neurons, which increase and decrease, respectively, their action potential frequency (APF) as extracellular glucose levels increase throughout the physiological range. Glucose-inhibited neurons were found predominantly in the medial ARC, whereas glucose-excited neurons were found in the lateral ARC. ARC glucose-excited neurons in brain slices dose-dependently increased their APF and decreased their ATP-sensitive K+ channel (KATP channel) currents as extracellular glucose levels increased from 0.1 to 10 mmol/l. However, glucose sensitivity was greatest as extracellular glucose decreased to <2.5 mmol/l. The glucokinase inhibitor alloxan increases KATP single-channel currents in glucose-excited neurons in a manner similar to low glucose. Leptin did not alter the activity of ARC glucose-excited neurons. Although insulin did not affect ARC glucose-excited neurons in the presence of 2.5 mmol/l (steady-state) glucose, they were stimulated by insulin in the presence of 0.1 mmol/l glucose. Neuropeptide Y (NPY) inhibited and alpha-melanocyte-stimulating hormone stimulated ARC glucose-excited neurons. ARC glucose-excited neurons did not show pro-opiomelanocortin immunoreactivity. These data suggest that ARC glucose-excited neurons may serve an integrative role in the regulation of energy balance.
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PMID:The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. 1527 73

Selenium deficiency causes oxidative stress and impairs steroidogenesis in vitro. Leptin is closely related to the hypothalamo-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis at the central level while corticosteroids have been shown to stimulate leptin secretion in most studies. We hypothesized that oxidative stress impairs adrenal steroidogenesis and decreases leptin production in vivo. The goal of this study was to investigate in rats the effects of selenium deficiency and oxidative stress on adrenal function and on leptin concentrations. Weanling rats were fed a selenium-deficient (Se-) or selenium-sufficient (Se+) diet for 4-10 weeks. Selenium deficiency caused a marked decrease in liver (> or = 99%) and adrenal (> or = 81%) glutathione peroxidase (GPx) activities. Selenium deficiency did not affect basal and short-term adrenocorticotropin (ACTH) stimulated corticosterone or leptin concentrations. In contrast, after long-term ACTH stimulation, selenium deficiency caused a doubling in adrenal isoprostane content and blunted the increase in corticosterone and leptin concentrations observed in Se+ animals. Plasma leptin concentrations were 50% lower in Se- compared to Se+ animals following long-term ACTH. Our results suggest that oxidative stress causes a decrease in circulating corticosterone in response to ACTH, and, as a consequence, a decrease in plasma leptin concentrations.
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PMID:Selenium deficiency impairs corticosterone and leptin responses to adrenocorticotropin in the rat. 1532 34

Alcohol intake is known to modulate plasma concentrations of neuroendocrine peptides. However, recent results suggest that the endocrine system may not only respond passively to alcohol intake but that, vice versa, it also actively modulates alcohol intake behaviour. The most coherent body of data concerns the hypothalamo-pituitary-adrenocortical (HPA) axis, with low corticotrophin-releasing hormone (CRH) being associated with more intense craving and increased probability of relapse after acute detoxification. Leptin, beta-endorphin and atrial natriuretic peptide (ANP), which indirectly regulate the HPA system, also may modulate the intensity of craving or the intensity of the alcohol withdrawal syndrome. Although most of the currently available data demonstrate association rather than causality between neuroendocrine changes and alcohol-related behaviours, they do provide testable hypotheses and open up perspectives of treating alcohol dependence via manipulation of the neuroendocrine axis.
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PMID:Neuroendocrine pathways of addictive behaviour. 1551 14

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

While there have been many studies in various species examining the mode of central leptin action on food intake, there is however a paucity of data in birds. We have, therefore, addressed this issue in broiler chickens because this strain was selected for high growth rate, hence high food intake. Continuous infusion of recombinant chicken leptin (8 microg/kg/h) during 6 h at a constant rate of 3 ml/h resulted in a significant reduction (49-57%) of food intake in 3-week-old broiler chickens (P < 0.05). The effect of leptin within the central nervous system (CNS) was mediated via selective hypothalamic neuropeptides. Leptin significantly decreased the expression of its receptor (Ob-R), neuropeptide Y (NPY), orexin (ORX), and orexin receptor (ORXR) (P < 0.05), but not that of agouti-related protein (AgRP) (anabolic/orexigenic effectors) in chicken hypothalamus. However, the catabolic/anorexigenic neuropeptides namely proopiomelanocortin (POMC) and corticotropin-releasing hormone (CRH) mRNA levels remained unchanged after leptin treatment. Despite the absence of leptin effect on AgRP (the antagonist of melanocortin receptor MCR) and POMC (the precursor of alpha-melanocyte stimulating hormone which is a potent agonist for MCR), leptin significantly decreased the expression of MCR-4/5 gene in chicken hypothalamus (P < 0.05) suggesting that leptin acts directly (as ligand) or indirectly (via other ligands) on MCRs to regulate food intake in birds. Additionally, leptin down-regulated the expression of fatty acid synthase (FAS) gene in chicken hypothalamus, indicating an additional pathway of leptin action on food intake such as described for FAS inhibitors. These findings provide new insight into the mechanism of leptin control of food intake in chickens.
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PMID:Mode of leptin action in chicken hypothalamus. 1590 12

Leptin gains access to the central nervous system where it influences activity of neuronal networks involved in ingestive behavior, neuroendocrine activity, and metabolism. In particular, the brain melanocortin (MC) system is important in leptin signaling and maintenance of energy balance. Although leptin or MC receptor insensitivity has been proposed to be associated with obesity, the present study compared central leptin and MC receptor stimulation on some of the above-mentioned parameters and investigated whether these treatments predict proneness to diet-induced obesity (DIO) in outbred Wistar rats. Third-cerebroventricular administration of equi-anorexigenic doses of leptin and of the MC agonist melanotan-II caused comparable increases in plasma ACTH and corticosterone levels and c-Fos-labeling in approximately 70% of paraventricular hypothalamic (PVN) neuronal cell bodies containing CRH. This reinforces involvement of paraventricular CRH neurons in the short-term neuroendocrine and ingestive effects of leptin and melanocortins. In the DIO prediction study, anorexigenic efficacy of melanotan-II was not correlated with any parameter linked to DIO but was highly correlated with MC in situ binding (with labeled [Nle(4),D-Phe(7)]alpha-MSH) as well as CRH immunoreactivity in the PVN of DIO rats. This suggests intricate relationships among MC signaling, the CRH system, and ingestive behavior unrelated to DIO. In the same animals, leptin's anorexigenic efficacy was not correlated with PVN MC in situ binding or CRH immunoreactivity but correlated inversely to post-DIO plasma leptin, liver weight, and abdominal adiposity, the latter being correlated to insulin resistance. Thus, differences in leptin but not MC signaling might underlie DIO, visceral obesity, and insulin resistance.
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PMID:Reduced anorexigenic efficacy of leptin, but not of the melanocortin receptor agonist melanotan-II, predicts diet-induced obesity in rats. 1616 22

Adipose tissue plays a crucial role in energy homeostasis not only in storing triglyceride, but also responding to nutrient, neural, and hormonal signals, and producing factors which control feeding, thermogenesis, immune and neuroendocrine function, and glucose and lipid metabolism. Adipose tissue secretes leptin, steroid hormones, adiponectin, inflammatory cytokines, resistin, complement factors, and vasoactive peptides. The endocrine function of adipose tissue is typified by leptin. An increase in leptin signals satiety to neuronal targets in the hypothalamus. Leptin activates Janus-activating kinase2 (Jak2) and STAT 3, resulting in stimulation of anorexigenic peptides, e.g., alpha-MSH and CART, and inhibition of orexigenic peptides, e.g., NPY and AGRP. The reduction in leptin levels during fasting stimulates appetite, decreases thermogenesis, thyroid and reproductive hormones, and increases glucocorticoids. Leptin also stimulates fatty acid oxidation, insulin release, and peripheral insulin action. These effects involve regulation of PI-3 kinase, PTP-1B, suppressor of cytokine signaling-3 (SOCS-3), and AMP-activated protein kinase in the brain and peripheral organs. There is emerging evidence that leptin, adiponectin, and resistin act through overlapping pathways. Understanding the signal transduction of adipocyte hormones will provide novel insights on the pathogenesis and treatment of obesity, diabetes, and various metabolic disorders.
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PMID:Adipokines that link obesity and diabetes to the hypothalamus. 1687 74


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