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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A regular daily meal regimen, as opposed to ad libitum consumption, enforces eating at a predefined time and within a short timeframe. Hence, it is important to study food intake regulation in animal feeding models that somewhat reflect this pattern. We investigated the effect of scheduled feeding on the intake of a palatable, high-sugar diet in rats and attempted to define central mechanisms - especially those related to opioid signaling--responsible for overeating sweet foods under such conditions. We found that scheduled access to food, even as challenging as 20 min per day, does not prevent overconsumption of a high-sucrose diet compared to a standard one. An opioid receptor antagonist, naloxone, at 0.3-1 mg/kg b. wt., decreased the intake of the sweet diet, whereas higher doses were required to reduce bland food consumption. Real-time PCR analysis revealed that expression of hypothalamic and brainstem genes encoding opioid peptides and receptors did not differ in sucrose versus regular diet-fed rats, which suggests that scheduled intake of sweet food produces only a transient change in the opioid tone. Intake of sugar was also associated with upregulation of orexin and oxytocin genes in the hypothalamus and NPY in the brainstem. We conclude that scheduled consumption of sugar diets is associated with activity of a complex network of neuroregulators involving opioids, orexin, oxytocin and NPY.
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PMID:Complexity of neural mechanisms underlying overconsumption of sugar in scheduled feeding: involvement of opioids, orexin, oxytocin and NPY. 1902 8

In North American society, it is all too common for the intake of calories to outweigh an individual's energy demands. Such over-consumption where high-energy foods are readily available undoubtedly contributes to the growing problem of obesity. Palatable food stimulates brain circuits similar to those that mediate behavioral responses to drugs of abuse, which may underlie the continuation of food intake long after energy requirements are met. Among the brain areas implicated in reward and food intake, the lateral hypothalamus (LH) has long been recognized as a common region involved in both. It has been suggested that orexin neurons that are expressed exclusively within and adjacent to the LH comprise a major cellular substrate for the functioning of the LH. Here, we review the idea that the orexin neuropeptides play a key role in the rewarding aspects of food intake through interactions with both peripheral and central signals reflecting current energy stores as well as the classic reward pathway--the mesolimbic dopamine system. Furthermore, a possible heterogeneity of orexin neurons is discussed. Uncovering orexin's role in food reinforcement may provide insight into hyperphagia and obesity. In addition, the idea that food intake and substance abuse involve similar brain circuitry suggests potential for a single treatment aiding both obesity and addiction.
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PMID:Interaction between orexins and the mesolimbic system for overriding satiety. 1954 24

Recent studies in normal-weight rats have linked circulating triglycerides (TG), when elevated by a high-fat (HF) compared to equicaloric low-fat (LF) meal, to an increase in subsequent food intake and hypothalamic expression of orexigenic peptides. The present study tested whether natural variations between rats in their TG levels after a small HF meal can also be related to their individual patterns of eating and peptide expression. In tail vein blood collected on three separate days 60 min after a HF meal, levels of TG were found to be strongly, positively correlated within rats from day to day but were highly variable between rats (75-365 mg/dl), allowing distinct subgroups (33% lowest or highest) to be formed. Compared to "Low-TG responders" with post-meal levels averaging 109 mg/dl, "High-TG responders" with 240 mg/dl showed in two separate experiments a significant increase in caloric intake in a subsequent laboratory chow meal. Before this larger meal, these rats with elevated TG consistently exhibited higher expression levels and synthesis of the orexigenic peptides, enkephalin, orexin and melanin-concentrating hormone, as revealed using real-time quantitative PCR, radiolabeled in situ hybridization, and immunofluorescence histochemistry. Over the long-term, the High-TG responders also showed an increased propensity to overeat, gain weight and accumulate excess body fat on a chronic HF diet. This simple measure of TG levels after a HF meal may offer a useful tool for identifying subpopulations with increased risk for overeating and dietary obesity and detecting early signs of brain disturbances that may contribute to this high-risk phenotype.
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PMID:Circulating triglycerides after a high-fat meal: predictor of increased caloric intake, orexigenic peptide expression, and dietary obesity. 1966 14

Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.
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PMID:Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation. 2005 29

Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
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PMID:Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity. 2033 86

Hypothalamic pro-opiomelanocortin (POMC) activity is reportedly essential for satiety signalling downstream of serotonin (5-HT). Here we show that food-restricted wild-type mice, which exhibited decreased hypothalamic POMC expression and increased hypothalamic orexin expression, were responsive to m-chlorophenylpiperazine (m-CPP), a 5-HT(2C/1B) receptor agonist, leading to anorexia, whereas food-restricted A(y) mice with decreased hypothalamic POMC and orexin expression, were not. Injection of POMC small interfering RNA (siRNA) oligonucleotide+orexin siRNA oligonucleotide into the third cerebral ventricle was unresponsive to mCPP-induced anorexia, whereas a single injection of POMC or orexin siRNA oligonucleotides elicited a response. The injection of POMC siRNA oligonucleotides suppressed the anorexic effects of sibutramine, a serotonin and noradrenaline re-uptake inhibitor. The injection of orexin siRNA oligonucleotides suppressed the hyperphagia induced by the injection of POMC siRNA oligonucleotides. These findings suggest that functional hypothalamic POMC and orexin activity has a critical role in satiety signalling of mCPP in mice.
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PMID:Hypothalamic orexin and pro-opiomelanocortin activities are essential for the anorexic effects of m-chlorophenylpiperazine in mice. 2058 30

The goal of this study is to examine the expression pattern of orexigenic peptides, orexin (OX) and melanin-concentrating hormone (MCH), in the perifornical lateral hypothalamus (PFLH) in subpopulations of Sprague-Dawley rats differing in their propensity to overconsume a high-fat diet. Immediately after an initial 5-day screening test that predicts long-term consumption, rats identified as high-fat consumers (HFC), ingesting 35% more calories of a high-fat relative to low-fat chow diet, had significantly elevated mRNA expression of OX in the perifornical but not lateral hypothalamic area and of MCH mRNA in both areas, when compared to control rats that consume similar amounts of these diets. This same OX and MCH expression pattern was seen in HFC rats maintained for two weeks on a low-fat chow diet, indicating that increased expression of these orexigenic peptides, occurring independently of the high-fat diet, may be an inherent characteristic of these rats. These HFC rats were also more active and slightly more anxious than controls, as measured by line crossings and time spent in the periphery or middle segments of an open field. Together, these results demonstrate that animals prone to overeating a high-fat diet show a baseline increase in orexigenic peptide expression in the PFLH along with higher behavioral arousal, which together may contribute to their increased consummatory behavior.
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PMID:Increased orexin and melanin-concentrating hormone expression in the perifornical lateral hypothalamus of rats prone to overconsuming a fat-rich diet. 2060 Feb 43

Lactation is an important physiological model of the integration of energy balance and reproduction, as it involves activation of potent appetitive neuropeptide systems coupled to a profound inhibition of pulsatile GnRH/LH secretion. There are multiple systems that contribute to the chronic hyperphagia of lactation: 1) suppression of the metabolic hormones, leptin and insulin, 2) activation of hypothalamic orexigenic neuropeptide systems NPY, AGRP, orexin (OX) and melanin concentrating hormone (MCH), 3) special induction of NPY expression in the dorsomedial hypothalamus, and 4) suppression of anorexigenic systems POMC and CART. These changes ensure adequate energy intake to meet the metabolic needs of milk production. There is significant overlap in all of the systems that regulate food intake with the regulation of GnRH, suggesting there could be several redundant factors acting to suppress GnRH/LH during lactation. In addition to an overall increase in inhibitory tone acting directly on GnRH cell bodies that is brought about by increases in orexigenic systems, there are also effects at the ARH to disrupt Kiss1/neurokinin B/dynorphin neuronal function through inhibition of Kiss1 and NKB. These changes could lead to an increase in inhibitory auto-regulation of the Kiss1 neurons and a possible disruption of pulsatile GnRH release. While the low levels of leptin and insulin contribute to the changes in ARH appetitive systems, they do not appear to contribute to the suppression of ARH Kiss1 or NKB. The inhibition of Kiss1 may be the key factor in the suppression of GnRH during lactation, although the mechanisms responsible for its inhibition are unknown.
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PMID:The neuroendocrine basis of lactation-induced suppression of GnRH: role of kisspeptin and leptin. 2072 62

Data suggest that low levels of dopamine D2 receptors and attenuated responsivity of dopamine-target regions to food intake is associated with increased eating and elevated weight. There is also growing (although mixed) evidence that genotypes that appear to lead to reduced dopamine signaling (e.g., DRD2, DRD4, and DAT) and certain appetite-related hormones and peptides (e.g., ghrelin, orexin A, leptin) moderate the relation between dopamine signaling, overeating, and obesity. This chapter reviews findings from studies that have investigated the relation between dopamine functioning and food intake and how certain genotypes and appetite-related hormones and peptides affect this relation.
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PMID:Dopamine-based reward circuitry responsivity, genetics, and overeating. 2124 71

Historically, studies of food intake regulation started with the hypothalamus and gradually expanded to mesocorticolimbic regions, while studies of drug use began with mesocorticolimbic regions and now include the hypothalamus. As research on ingestive behavior has progressed, it has uncovered more and more similarities between the regulation of palatable food and drug intake. It has also identified specific neurochemicals involved in palatable food and drug intake. Hypothalamic orexigenic neurochemicals specifically involved in controlling fat ingestion, including galanin, enkephalin, orexin and melanin-concentrating hormone, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Research in Bart Hoebel's laboratory in conjunction with our own has shown that consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Both fat and ethanol intake are also regulated by dopamine and acetylcholine acting in mesocorticolimbic nuclei. This close relationship of fat and ethanol is likely driven in part by circulating lipids, which are increased by fat and ethanol intake, known to increase expression and levels of the neurochemicals, and found to promote further intake of fat and ethanol. Compellingly, recent studies suggest that these systems may already be dysregulated in animals prone to consuming excess fat or ethanol, even before they have ever been exposed to these substances. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse.
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PMID:Similarities in hypothalamic and mesocorticolimbic circuits regulating the overconsumption of food and alcohol. 2154 31


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