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)

Central neuropeptide Y (NPY) injection has been reported to cause hyperphagia and in some cases also hypometabolism or hypothermia. Chronic central administration induced a moderate rise of short duration in body weight, without consistent metabolic/thermal changes. In the present studies the acute and subsequent subacute ingestive and metabolic/thermal changes were studied following intracerebroventricular (i.c.v.) injections of NPY in cold-adapted and non-adapted rats, or the corresponding chronic changes following i.c.v. NPY infusion. Besides confirming basic earlier data, we demonstrated novel findings: a temporal relationship for the orexigenic and metabolic/thermal effects, and differences of coordination in acute/subacute/chronic phases or states. The acute phase (30-60 min after injection) was anabolic: coordinated hyperphagia and hypometabolism/hypothermia. NPY evoked a hypothermia by suppressing any (hyper)metabolism in excess of basal metabolic rate, without enhancing heat loss. Thus, acute hypothermia was observed in sub-thermoneutral but not thermoneutral environments. The subsequent subacute catabolic phase exhibited opposite effects: slight increase in metabolic rate, rise in body temperature, reaching a plateau within 3-4 h after injection -- this was maintained for at least 24 h; meanwhile the food intake decreased and the normal daily weight gain stopped. This rebound is only indirectly related to NPY. Chronic (7-day long) i.c.v. NPY infusion induced an anabolic phase for 2-3 days, followed by a catabolic phase and fever, despite continued infusion. In cold-adaptation environment the primary metabolic effect of the infusion induced a moderate hypothermia with lower daytime nadirs and nocturnal peaks of the circadian temperature rhythm, while at near-thermoneutral environments in non-adapted rats the infusion attenuated only the nocturnal temperature rise by suppressing night-time hypermetabolism. Further finding is that in cold-adapted animals, the early feeding effect of NPY-infusion was enhanced, whereas the early hypothermic effect in cold was limited by interference with competing thermoregulatory mechanisms.
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PMID:Acute, subacute and chronic effects of central neuropeptide Y on energy balance in rats. 1575 44

Hyperphagia followed both central neuropeptide Y (NPY) administration and the presumed increase of endogenous NPY activity after food deprivation. NPY induced greater hyperphagia in cold-adapted than non-adapted rats; fasting of comparable severity caused similar hyperphagia in the two groups. NPY-receptor-antagonist D-Tyr(27,36), D-Thr32-NPY(27,36) or functional NPY-antagonist D-myo-inositol-1,2,6-trisphosphate attenuated the hyperphagic effect of both NPY and fasting in non-adapted rats. However, while completely preventing the NPY-hyperphagia, they did not influence the fasting-induced hyperphagia in cold-adapted rats. With cold-adaptation the sensitivity to NPY and to its antagonists increases, but the hypothalamic NPY loses from its fundamental role in the regulation of food intake, and the hyperphagia seen in cold-adaptation may need some other explanation.
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PMID:Effects of neuropeptide Y antagonists on food intake in rats: differences with cold-adaptation. 1604 Jan 56

We report a case of type 2 diabetes mellitus presenting hypothyroidism due to overeating of seaweed that was noticed as a result of a discrepancy between glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was undergoing managed treatment with oral medicines and insulin for diabetes mellitus with no sign of thyroid disease. Her thyroid function was euthyroid without aid of thyroid hormone. All of the patient's thyroid autoantibodies were negative. Fifteen weeks prior to indications of hypothyroidism, she had started to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame" seaweed every morning. Just before admission to our hospital, her GA was 26.9%, while GHb and fasting plasma glucose remained within normal ranges (less than 5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our attention to the development of complications. Naive interview of the patient led us to believe a thyroid hormone deficiency existed, though without any related complaints or findings, such as non-pitting edema, cold intolerance, or easy fatiguing. Seaweed consumption was stopped and periodic observation of thyroid function started. As thyroid hormone levels moved into normal range, GA and GHb returned to their normal relative ratio after 3 months. Thus, measurement of the relative ratio of GA and GHb may be useful for glycemic monitoring, with the potential as a readily available glycemic control marker for patients with changeable complications.
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PMID:A case of type 2 diabetes mellitus developing hypothyroidism discovered as a result of a discrepancy between glycated hemoglobin and glycated albumin values. 1611 42

Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with beta3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of beta3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a beta3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of beta3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.
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PMID:Indispensable role of mitochondrial UCP1 for antiobesity effect of beta3-adrenergic stimulation. 1636 88

Among polygenic mouse models of obesity, the New Zealand obese (NZO) mouse exhibits the most severe phenotype, with fat depots exceeding 40% of total body weight at the age of 6 mo. Here we dissected the components of energy balance including feeding behavior, locomotor activity, energy expenditure, and thermogenesis compared with the related lean New Zealand black (NZB) and obese B6.V-Lep(ob)/J (ob/ob) strains (11% and 65% fat at 23 wk, respectively). NZO mice exhibited a significant hyperphagia that, when food intake was expressed per metabolic body mass, was less pronounced than that of the ob/ob strain. Compared with NZB, NZO mice exhibited increased meal frequency, meal duration, and meal size. Body temperature as determined by telemetry with implanted sensors was reduced in NZO mice, but again to a lesser extent than in the ob/ob strain. In striking contrast to ob/ob mice, NZO mice were able to maintain a constant body temperature during a 20-h cold exposure, thus exhibiting a functioning cold-induced thermogenesis. No significant differences in spontaneous home cage activity were observed among NZO, NZB, and ob/ob strains. When mice had access to voluntary running wheels, however, running activity was significantly lower in NZO than NZB mice and even lower in ob/ob mice. These data indicate that obesity in NZO mice, just as in humans, is due to a combination of hyperphagia, reduced energy expenditure, and insufficient physical activity. Because NZO mice differ strikingly from the ob/ob strain in their resistance to cold stress, we suggest that the molecular defects causing hyperphagia in NZO mice are located distal from leptin and its receptor.
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PMID:Hyperphagia, lower body temperature, and reduced running wheel activity precede development of morbid obesity in New Zealand obese mice. 1661 59

Smith-Magenis syndrome (SMS) is a multisystem disorder characterized by developmental delay and mental retardation, a distinctive behavioral phenotype, and sleep disturbance. We undertook a comprehensive meta-analysis to identify genotype-phenotype relationships to further understand the clinical variability and genetic factors involved in SMS. Clinical and molecular information on 105 patients with SMS was obtained through research protocols and a review of the literature and analyzed using Fisher's exact test with two-tailed p values. Several differences in these groups of patients were identified based on genotype and gender. Patients with RAI1 mutation were more likely to exhibit overeating, obesity, polyembolokoilamania, self-hugging, muscle cramping, and dry skin and less likely to have short stature, hearing loss, frequent ear infections, and heart defects when compared with patients with deletion, while a subset of small deletion cases with deletions spanning from TNFRSF13B to MFAP4 was less likely to exhibit brachycephaly, dental anomalies, iris abnormalities, head-banging, and hyperactivity. Significant differences between genders were also identified, with females more likely to have myopia, eating/appetite problems, cold hands and feet, and frustration with communication when compared with males. These results confirm previous findings and identify new genotype-phenotype associations including differences in the frequency of short stature, hearing loss, ear infections, obesity, overeating, heart defects, self-injury, self-hugging, dry skin, seizures, and hyperactivity among others based on genotype. Additional studies are required to further explore the relationships between genotype and phenotype and any potential discrepancies in health care and parental attitudes toward males and females with SMS.
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PMID:Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases. 1753 3

Signal transducers and activators of transcription (STATs) are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5), the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF.
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PMID:Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity. 1828 95

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.
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PMID:SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice. 1832 30

p70 S6 kinase 1 (S6K) is a major downstream effector of the mammalian target of rapamycin (mTOR), primarily implicated in the control of protein synthesis, cell growth, and proliferation. Here we demonstrate that specific bidirectional molecular targeting of mediobasal hypothalamic (MBH) S6K activity in rats is sufficient to significantly alter food intake, body weight, hypothalamic orexigenic neuropeptide expression, hypothalamic leptin sensitivity, and the metabolic and feeding responses to a fast. In addition, adenoviral-mediated constitutive activation of MBH S6K improved cold tolerance and protected against high-fat diet-induced overeating, fat deposition, and insulin resistance. Our results provide direct evidence that MBH S6K activity bidirectionally drives behavioral and metabolic determinants of energy balance and promote the assessment of MBH S6K activity as a therapeutic target in metabolic diseases.
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PMID:Mediobasal hypothalamic p70 S6 kinase 1 modulates the control of energy homeostasis. 1904 62

In most mammals, maternal body mass and fat mass increase during pregnancy due to hyperphagia. These physiological changes provide the fetus with energy and nutrients and prepare the mother for the high energetic demands of lactation. In the present study, metabolic changes in response to cold and pregnancy were examined in female Brandt's voles (Lasiopodomys brandtii). At 23+/-1 degrees C, the voles increased body mass and deposited body fat during pregnancy. However, at 5+/-1 degrees C pregnant voles did not deposit body fat even though energy intake increased above the level in the warm. Serum leptin concentration increased during pregnancy and was not influenced by cold exposure. Thermogenic capacity, as indicated by uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT), increased in cold-exposed pregnant voles. The number and mass of fetuses were not affected by cold exposure. Our data may indicate the importance of an increased serum leptin concentration for a successful outcome of the pregnancy and also the independence of leptin secretion from body fat in pregnant voles. It also implies the need to develop central leptin resistance with respect to control of energy balance for pregnant voles.
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PMID:Cold exposure does not decrease serum leptin concentration, but increases energy intake and thermogenic capacity in pregnant Brandt's voles (Lasiopodomys brandtii). 1923 Nov 44


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