Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is a potent orexigenic agent capable of producing hyperphagia and obesity. NPY-containing neurons project from the hypothalmic arcuate nucleus to the paraventricular nucleus, an area known to be sensitive to the orexigenic effects of NPY. In this study we investigated the possibility that preproNPY messenger RNA (mRNA) content may be altered in obese Zucker rats compared to that of their lean littermates. Total RNA was isolated from hypothalamic dissections from male and female, obese and lean Zucker rats. RNA was also isolated from dissections of: olfactory bulb, entorhinal cortex, hippocampus, and striatum of female obese and lean rats. PreproNPY mRNA content was determined by solution hybridization-RNase protection analysis. The results revealed a 2- to 3-fold increase in preproNPY mRNA levels in the hypothalamus of obese animals compared to lean. The increase was observed in both sexes and was specific to the hypothalamus. In situ hybridization localized this increase to the arcuate nucleus. An additional RNase protection study was pursued to investigate the effects of 72 h food deprivation on hypothalamic preproNPY mRNA levels in lean and obese animals. Lean animals displayed an approximate 2-fold increase in preproNPY mRNA content, whereas obese animals showed no significant increase after food deprivation. These data are consistent with the hypothesis that NPY projections within the hypothalamus are involved in regulating feeding behavior and weight gain, and that disturbed regulation of hypothalamic NPY expression may play a role in the etiology of obesity in the genetically obese Zucker rat.
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PMID:Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. 237 52

Hyperphagia and obesity can be experimentally induced in rodents by microinjection of 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle (VNAB) to interrupt efferent catecholaminergic pathways to the hypothalamus. Since hypothalamic neuropeptide Y (NPY) is implicated in the control of ingestive behavior, we evaluated hypothalamic NPY activity in this model of obesity. Adult male rats injected bilaterally with 12 microg of 6-OHDA in the VNAB displayed an enhanced rate of body weight gain and selective dark-phase hyperphagia that started at about 10 days postinjection and persisted for the entire duration of the experiment. NPY gene expression, assessed by ribonuclease protection assay, was significantly higher in the hypothalami of 6-OHDA-treated hyperphagic rats during the dark phase (p < 0.01 vs. levels during the light phase and in control, vehicle-injected rats). We also evaluated gene expression of NPY Y and Y5 receptors, receptor subtypes reported to mediate NPY-induced feeding. The dark-phase increase in NPY mRNA was accompanied by the concomitant upregulation of NPY Y5R gene expression, but not of Y1R mRNA levels. Leptin, the peripheral hormone secreted by adipocytes, is believed to maintain body weight and inhibit food intake, most likely by suppressing hypothalamic NPY activity. Evaluation of leptin gene expression in the epididymal fat revealed that the upregulation of leptin mRNA noted during the dark phase in control rats did not occur in 6-OHDA-treated rats. These observations implied that the normal restraint on NPY and feeding exercised by leptin in control rats may be abrogated in 6-OHDA-treated hyperphagic rats due to insufficient levels of leptin. If so, administration of leptin should inhibit food intake in these rats. Indeed, injection of leptin (2 mg/kg, intraperitoneally (i.p.)) on 2 consecutive days reduced 24-h food intake by 25% and significantly reduced body weight. These results suggest that the nocturnal hyperphagia and resultant obesity induced by 6-OHDA injected into the VNAB may be attributed to leptin deficiency concomitant with increased hypothalamic NPY.
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PMID:Evidence that dark-phase hyperphagia induced by neurotoxin 6-hydroxydopamine may be due to decreased leptin and increased neuropeptide Y signaling. 961 6

Hypothalamic neuropeptides play critical roles in the regulation of appetite and body weight. We recently reported that disruption of neural signaling in the ventromedial nucleus (VMN) by microinjection of the neurotoxin, colchicine (COL), produced transient hyperphagia with attendant body weight gain lasting for 4 days. The neural mechanism(s) underlying this temporary shift in energy homeostasis is still unknown. Galanin (GAL) is produced in several hypothalamic nuclei and since microinjection of GAL into these sites stimulates feeding, we tested the hypothesis that galaninergic signaling is upregulated in COL-treated rats. COL (4 microgram in 0.5 microliter saline) or saline alone was microinjected into the VMN of adult male rats and GAL mRNA was evaluated in the basal hypothalamus by ribonuclease protection assay on day 1, day 2 and day 4 after injection. Whereas in saline-treated rats body weight and GAL mRNA remained unaffected, they were significantly increased in COL-injected rats through the period of observation. To identify the specific neuronal subpopulations involved, GAL mRNA levels were analyzed in feeding-related hypothalamic nuclei using semiquantitative in situ hybridization histochemistry on day 4 after microinjection of COL or saline into the VMN. In COL-treated rats, GAL mRNA levels increased dramatically over controls in the supraoptic nucleus, paraventricular nucleus (PVN), dorsomedial nucleus (DMN), arcuate nucleus (ARC) and lateral hypothalamic area (LHA); no significant change was observed in the central nucleus of amygdala. These results indicated that disruption of neurotransmission in the VMN upregulated GAL gene expression in those hypothalamic sites (PVN, DMN, LHA and ARC) that are implicated in regulation of feeding, and since GAL stimulates feeding, this neurochemical rearrangement may contribute to the over-eating in these animals. These results also suggest that, normally, neurons in the VMN may suppress GAL neurotransmission in feeding-regulating hypothalamic neural circuits.
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PMID:Disruption of neural signaling within the hypothalamic ventromedial nucleus upregulates galanin gene expression in association with hyperphagia: an in situ hybridization analysis. 988 30

The neural mechanisms involved in the compensatory hyperphagia exhibited by many vertebrate species after a fast are not fully understood but, in mammals, appear to involve nutritionally-sensitive neurons that co-express neuropeptide Y (NPY) and agouti-related protein (AGRP) in the infundibular hypothalamus. We investigated whether these neurons have been evolutionarily conserved in a non-mammalian vertebrate, the Japanese quail. Birds exhibited compensatory hyperphagia 1 h after return of food following a 24-h fast. We addressed a potential regulatory role for NPY, first, by using in situ hybridisation (ISH) to map NPY gene expression in the hypothalamus. This revealed a strong signal in the infundibular nucleus (IN). Secondly, we quantified NPY gene expression in 24-h fasted birds compared to ad libitum fed controls using two independent methods. In whole hypothalamus, measured by ribonuclease protection assay, NPY mRNA increased 1.5-fold in fasted birds. A similar, 1.7-fold, increase was observed specifically in the IN when analysed by ISH. No differences in NPY expression between fed and fasted birds were observed in other brain regions. To determine whether NPY neurons in the avian IN co-express AGRP, we cloned a fragment of the quail AGRP gene and used it to localise AGRP mRNA by ISH. The gene was expressed exclusively in the hypothalamus, specifically in the IN, where its distribution matched that of NPY. Double-label ISH revealed that the majority of NPY neurons in the IN co-express AGRP mRNA. Collectively, these data indicate that this cell type has been neuroanatomically and functionally conserved during vertebrate evolution.
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PMID:Neurons expressing neuropeptide Y mRNA in the infundibular hypothalamus of Japanese quail are activated by fasting and co-express agouti-related protein mRNA. 1200 19

The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons.
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PMID:Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness. 2559 82