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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.
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PMID:Hypothalamic CART is a new anorectic peptide regulated by leptin. 959 Jun 91

A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. Leptin, a hormone secreted by fat cells, acts in rodents via hypothalamic receptors to inhibit feeding and increase thermogenesis. A feedback regulatory loop with three distinct steps has been identified: (1) a sensor (leptin production by adipose cells) monitors the size of the adipose tissue mass; (2) hypothalamic centers receive and integrate the intensity of the leptin signal through leptin receptors (LRb); (3) effector systems, including the sympathetic nervous system, control the two main determinants of energy balance-energy intake and energy expenditure. While this feedback regulatory loop is well established in rodents, there are many unsolved questions about its applicability to body weight regulation in humans. The rate of leptin production is related to adiposity, but a large portion of the interindividual variability in plasma leptin concentration is independent of body fatness. Gender is an important factor determining plasma leptin, with women having markedly higher leptin concentrations than men for any given degree of fat mass. The ob mRNA expression is also upregulated by glucocorticoids, whereas stimulation of the sympathetic nervous system results in its inhibition. Furthermore, leptin is not a satiety factor in humans because changes in food intake do not induce short-term increases in plasma leptin levels. After its binding to LRb in the hypothalamus, leptin stimulates a specific signaling cascade that results in the inhibition of several orexigenic neuropeptides, while stimulating several anorexigenic peptides. The orexigenic neuropeptides that are downregulated by leptin are NPY (neuropeptide Y), MCH (melanin-concentrating hormone), orexins, and AGRP (agouti-related peptide). The anorexigenic neuropeptides that are upregulated by leptin are alpha-MSH (alpha-melanocyte-stimulating hormone), which acts on MC4R (melanocortin-4 receptor); CART (cocaine and amphetamine-regulated transcript); and CRH (corticotropin-releasing-hormone). Obese humans have high plasma leptin concentrations related to the size of adipose tissue, but this elevated leptin signal does not induce the expected responses (i.e., a reduction in food intake and an increase in energy expenditure). This suggests that obese humans are resistant to the effects of endogenous leptin. This resistance is also shown by the lack of effect of exogenous leptin administration to induce weight loss in obese patients. The mechanisms that may account for leptin resistance in human obesity include a limitation of the blood-brain-barrier transport system for leptin and an inhibition of the leptin signaling pathways in leptin-responsive hypothalamic neurons. During periods of energy deficit, the fall in leptin plasma levels exceeds the rate at which fat stores are decreased. Reduction of the leptin signal induces several neuroendocrine responses that tend to limit weight loss, such as hunger, food-seeking behavior, and suppression of plasma thyroid hormone levels. Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.
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PMID:Leptin signaling, adiposity, and energy balance. 1207 65

Energy homeostasis is controlled by a complex neuroendocrine system consisting of peripheral signals like leptin and central signals, in particular, neuropeptides. Several neuropeptides with anorexigenic (POMC, CART, and CRH) as well as orexigenic (NPY, AgRP, and MCH) actions are involved in this complex (partly redundant) controlling system. Starvation as well as overfeeding lead to changes in expression levels of these neuropeptides, which act downstream of leptin, resulting in a physiological response. In this review the role of several anorexigenic and orexigenic (hypothalamic) neuropeptides on food intake and body weight regulation is summarized.
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PMID:Neuropeptides, food intake and body weight regulation: a hypothalamic focus. 1253 10

Regulation of the hypothalamic-pituitary-thyroid (HPT) axis is dependent upon the secretion of thyrotropin-releasing hormone (TRH), a tripeptide originating in the hypothalamic paraventricular nucleus (PVN). These so-called hypophysiotropic neurons are under feedback inhibition by circulating levels of thyroid hormone, mediated through interactions with the beta2 thyroid hormone receptor (TRbeta2) and competition with the phosphorylated form of cyclic adenosine 5'-monophosphate response element binding protein (CREB) for a multifunctional binding site in the TRH gene. The non-thyroidal illness syndrome, characterized by low circulating thyroid hormone levels yet suppression of TRH gene expression in hypophysiotropic neurons, is due to alteration in the regulatory factors that modulate TRH gene expression to result in central hypothyroidism. These factors include alpha melanocyte-stimulating hormone (alphaMSH) and cocaine- and amphetamine-regulated transcript (CART), and agouti-related protein (AGRP) and neuropeptide Y (NPY), substances co-produced by distinct populations of leptin-responsive neurons in the hypothalamic arcuate nucleus. Through monosynaptic projections from arcuate nucleus neurons to hypophysiotropic TRH neurons, these factors contribute to suppression of HPT axis during fasting and starvation by exerting opposing actions on the TRH gene, altering the sensitivity for feedback inhibition by thyroid hormone. In contrast, central hypothyroidism associated with infection may be due to upregulation of type 2 deiodinase activity in tanycytes, specialized glial cells that line the infralateral walls and floor of the third ventricle. Through tanycyte-cerebrospinal fluid, -vascular or -neuronal associations, these cells may lead to inhibition of TRH gene expression in hypophysiotropic neurons by increasing local triiodothyronine production.
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PMID:Feedback regulation of thyrotropin-releasing hormone (TRH): mechanisms for the non-thyroidal illness syndrome. 1548 10

Anorexia (anx) is a recessive mutation that causes lethal starvation in homozygous mice. Studies of anx/anx mice hypothalamus have shown abnormalities in the orexigenic (NPY/AGRP neurons) and the anorexigenic (POMC/CART neurons) pathways. By gene expression profiling using cDNA and oligonucleotide microarrays, we have shown that a surexpression of genes involved in inflammatory process occurred in anx mice hypothalamus. This inflammatory process could be the cause of the anorexia phenotype observed in these mice.
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PMID:Gene expression profiling reveals an inflammatory process in the anx/anx mutant mice. 1600 7

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

We used three inbred rat strains known for significant differences in the activity and reactivity of their hypothalamic-pituitary-adrenal (HPA) axis to stress [Fischer 344 (F344), Brown Norway (BN) and Lewis (Lew) rats] to search for a strain difference in the paradoxical increase in running activity induced by food restriction and to explore the role of the HPA axis in this behaviour. Rats were randomly assigned to either an ad lib sedentary group (AL), a control wheel activity group (ACT), a food restriction-induced hyperactivity group (FR-ACT) group (1.5 h/day ad lib food, 22.5 h/day ad lib wheel access) or a pair-fed group (FR). The BN and Lew rats reached the 25% body weight-loss criterion of FR-ACT (strain effect: F(2,132) = 45.58, P < 10-6) faster than the F344 strain due to higher food restriction-induced running activity (strain effect: F(2,65) = 17.43, P = 0.00001). FR and FR-ACT decreased thymus weight (marker of integrated HPA axis activation) in all strains. In Lew and BN strains, FR-ACT induced a further decrement on thymus weight compared to their FR group. Prefeeding corticosterone levels (15.00 h) increased during the study in BN and Lew FR-ACT rats, but not in F344. Total wheel turns were correlated to both final adipose weight (r = -0.49, P = 0.002) and thymus weight decrement (r = 0.59, P = 0.0001), emphasizing the relationship between fat mass and HPA axis activation in excessive running activity. Increased running in conditions of food restriction and HPA axis activation may be linked at the level of the central nervous system. However, the involvement of corticotrophin-releasing hormone, agouti-related peptide or cocaine- and amphetamine-regulated transcript in behavioural disturbances of FR-ACT rats was excluded (in situ hybridization). We propose that corticosterone may be the link between initial low levels of fat mass and/or rate of fat mass loss (peripheral energy stores) and increased wheel activity, favouring fueling through lipolysis and proteolysis and reinforcing the self starvation via reward mechanisms, thus establishing a deleterious vicious cycle.
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PMID:Genetic differences in hypothalamic-pituitary-adrenal axis activity and food restriction-induced hyperactivity in three inbred strains of rats. 1621 3

Ghrelin is upregulated under negative energy balance conditions, including starvation and hypoglycemia, while it is downregulated under situations of positive energy balance, such as feeding, hyperglycemia and obesity. The aims of this study were to assess potential ghrelin interactions with glucose levels in appetite control and to identify potential mechanisms involving orexigenic and anorexigenic ghrelin mediated signals by using a specific anti-ghrelin antibody. Our results confirm that peripheral ghrelin is an important signal in meal initiation and food intake stimulation. C-fos positive neurons in the PVN increased after insulin or 2-deoxyglucose administration. Moreover, we also demonstrate that peripheral ghrelin blockade with a specific anti-ghrelin antibody reduces, in part, the orexigenic signal induced by insulin and 2-DG administration. Furthermore, when we blocked peripheral ghrelin, c-fos positive CRF neurons and CART expression increased in the PVN, both under hypoglycemia or cytoglycopenia conditions, suggesting a neuronal activation (anorexigenic signalling) in this hypothalamic region. In summary, our findings imply that peripheral ghrelin plays an important role in regulatory "glucostatic" feeding mechanisms due to its role as a "hunger" signal affecting the PVN area, which may contribute to energy homeostasis through both orexigenic/anorexigenic pathways.
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PMID:Peripheral ghrelin participates in glucostatic feeding mechanisms and in the anorexigenic signalling mediated by CART and CRF neurons. 1666 99

The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 +/- 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, R(p)-adenosine 3',5'-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic-pituitary-inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial alpha(1)-adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption.
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PMID:Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog. 1772 Jul 43

We tested the hypothesis that, in the amphibian Xenopus laevis, cocaine- and amphetamine-regulated transcript peptide (CARTp) not only has widespread actions in the brain but also acts as a local factor in endocrine pituitary cells and/or is neurohemally secreted into the circulation to control peripheral targets. CARTp-immunoreactive cells occur in the olfactory bulb, nucleus accumbens, amygdala, septum, striatum, nucleus of Bellonci, ventrolateral nucleus, central thalamic nucleus, preoptic nuclei, and suprachiasmatic nucleus, and particularly in the medial pallium, ventromedial nucleus, hypothalamus, Edinger-Westphal nucleus, optic tectum, raphe nuclei, central gray, nucleus of the solitary tract, and spinal cord. From the hypothalamic magnocellular nucleus, CARTp-containing axons run to the neurohemal median eminence, and to the neural pituitary lobe to form neurohemal terminals, as shown by immunoelectron microscopy. Starvation increases the number of CARTp-cells in the optic tectum by 46% but has no effect on such cells in the torus semicircularis. CARTp does not affect in vitro release of alpha-melanophore-stimulating hormone from pituitary melanotrope cells. Our results support the hypothesis that in X. laevis, CARTp not only has multiple and not exclusively feeding-related actions in the brain but is also secreted as a neurohormone 1) into the portal system to control endocrine targets in the pituitary distal lobe and 2) from neurohemal axon terminals in the neural pituitary lobe to act peripherally. The differences in CARTp distribution between X. laevis and Rana esculenta may be related to different environmental and physiological conditions such as feeding, sensory information processing, and locomotion.
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PMID:Brain distribution and evidence for both central and neurohormonal actions of cocaine- and amphetamine-regulated transcript peptide in Xenopus laevis. 1822 Feb 55


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