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Disease relevance of Hyperphagia


Psychiatry related information on Hyperphagia


High impact information on Hyperphagia


Chemical compound and disease context of Hyperphagia

  • Rats injected with p-chlorophenylalanine intraventricularly began overeating after 3 days and continued to display marked hyperphagia, primarily in the daytime, accompanied by increased body weight for 1 to 2 weeks [16].
  • Although the origin of the decreased basal glucose uptake remains unknown it might be related to a similar decrease in basal glucose uptake by ventromedial hypothalamic cells, an event presumably resulting in a tendency to hyperphagia [17].
  • Replacement of corticosterone in the drinking water of Pomc mice recapitulated the hyperphagia, excess weight gain and fat accumulation, and hyperleptinemia characteristic of genetically rescued PomcTg mice [18].
  • In lactating rats, another model of hyperphagia, cholesterol synthesis is increased 2.4-fold in midintestinal segments excluded from contact with the food stream and 2.9-fold in segments of the proximal intestine that have been bypassed [19].
  • Compared with control rats, STZ-induced diabetic rats had significant hyperphagia and weight loss [20].

Biological context of Hyperphagia

  • The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake [21].
  • Surprisingly, despite significant hyperphagia, Y2(-/-) Y4(-/-) mice retained a markedly lean phenotype, with reduced body weight, white adipose tissue mass, leptinemia, and insulinemia [22].
  • Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system [23].
  • The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia [24].
  • When c-Cbl(-/-) mice were fed a high-fat diet for 4 weeks, they maintained hyperphagia, higher whole-body oxygen consumption (27%), and greater activity (threefold) compared with wild-type animals fed the same diet [25].

Anatomical context of Hyperphagia


Gene context of Hyperphagia


Analytical, diagnostic and therapeutic context of Hyperphagia


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  2. Axon-sparing brain lesioning technique: the use of monosodium-L-glutamate and other amino acids. Simson, E.L., Gold, R.M., Standish, L.J., Pellett, P.L. Science (1977) [Pubmed]
  3. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Butler, A.A., Marks, D.L., Fan, W., Kuhn, C.M., Bartolome, M., Cone, R.D. Nat. Neurosci. (2001) [Pubmed]
  4. Adrenalectomy reduces neuropeptide Y-induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus. Wisialowski, T., Parker, R., Preston, E., Sainsbury, A., Kraegen, E., Herzog, H., Cooney, G. J. Clin. Invest. (2000) [Pubmed]
  5. Transplantable rat glucagonomas cause acute onset of severe anorexia and adipsia despite highly elevated NPY mRNA levels in the hypothalamic arcuate nucleus. Jensen, P.B., Blume, N., Mikkelsen, J.D., Larsen, P.J., Jensen, H.I., Holst, J.J., Madsen, O.D. J. Clin. Invest. (1998) [Pubmed]
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  8. Abnormal pituitary-adrenal responses to corticotropin-releasing hormone in patients with seasonal affective disorder: clinical and pathophysiological implications. Joseph-Vanderpool, J.R., Rosenthal, N.E., Chrousos, G.P., Wehr, T.A., Skwerer, R., Kasper, S., Gold, P.W. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
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  10. Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation. Pedrazzoli, M., D'Almeida, V., Martins, P.J., Machado, R.B., Ling, L., Nishino, S., Tufik, S., Mignot, E. Brain Res. (2004) [Pubmed]
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  12. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Kim, M.S., Park, J.Y., Namkoong, C., Jang, P.G., Ryu, J.W., Song, H.S., Yun, J.Y., Namgoong, I.S., Ha, J., Park, I.S., Lee, I.K., Viollet, B., Youn, J.H., Lee, H.K., Lee, K.U. Nat. Med. (2004) [Pubmed]
  13. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nonogaki, K., Strack, A.M., Dallman, M.F., Tecott, L.H. Nat. Med. (1998) [Pubmed]
  14. Cholecystokinin in the brains of obese and nonobese mice. Straus, E., Yalow, R.S. Science (1979) [Pubmed]
  15. Stress-induced hyperphagia and obesity in rats: a possible model for understanding human obesity. Rowland, N.E., Antelman, S.M. Science (1976) [Pubmed]
  16. Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine. Breisch, S.T., Zemlan, F.P., Hoebel, B.G. Science (1976) [Pubmed]
  17. Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice. Cuendet, G.S., Loten, E.G., Jeanrenaud, B., Renold, A.E. J. Clin. Invest. (1976) [Pubmed]
  18. Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice. Smart, J.L., Tolle, V., Low, M.J. J. Clin. Invest. (2006) [Pubmed]
  19. Cholesterol synthesis in bypassed segments of the small intestine in hyperphagic rats. Feingold, K.R., Zeng, Q.H., Soued, M., Moser, A.H. Gastroenterology (1989) [Pubmed]
  20. Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats. Namkoong, C., Kim, M.S., Jang, P.G., Han, S.M., Park, H.S., Koh, E.H., Lee, W.J., Kim, J.Y., Park, I.S., Park, J.Y., Lee, K.U. Diabetes (2005) [Pubmed]
  21. Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway. Forbes, S., Bui, S., Robinson, B.R., Hochgeschwender, U., Brennan, M.B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  22. Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice. Sainsbury, A., Baldock, P.A., Schwarzer, C., Ueno, N., Enriquez, R.F., Couzens, M., Inui, A., Herzog, H., Gardiner, E.M. Mol. Cell. Biol. (2003) [Pubmed]
  23. Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. Anai, M., Funaki, M., Ogihara, T., Kanda, A., Onishi, Y., Sakoda, H., Inukai, K., Nawano, M., Fukushima, Y., Yazaki, Y., Kikuchi, M., Oka, Y., Asano, T. Diabetes (1999) [Pubmed]
  24. Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. Havel, P.J., Hahn, T.M., Sindelar, D.K., Baskin, D.G., Dallman, M.F., Weigle, D.S., Schwartz, M.W. Diabetes (2000) [Pubmed]
  25. Casitas b-lineage lymphoma-deficient mice are protected against high-fat diet-induced obesity and insulin resistance. Molero, J.C., Waring, S.G., Cooper, A., Turner, N., Laybutt, R., Cooney, G.J., James, D.E. Diabetes (2006) [Pubmed]
  26. Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal. Evans, R.D., Williamson, D.H. Biochem. J. (1988) [Pubmed]
  27. Alterations in deprivation, glucoprivic and sucrose intake following general, mu and kappa opioid antagonists in the hypothalamic paraventricular nucleus of rats. Koch, J.E., Glass, M.J., Cooper, M.L., Bodnar, R.J. Neuroscience (1995) [Pubmed]
  28. Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats. Kalinichev, M., Rourke, C., Daniels, A.J., Grizzle, M.K., Britt, C.S., Ignar, D.M., Jones, D.N. Psychopharmacology (Berl.) (2005) [Pubmed]
  29. Effects of palatability-induced hyperphagia and food restriction on mRNA levels of neuropeptide-Y in the arcuate nucleus. Kim, E.M., Welch, C.C., Grace, M.K., Billington, C.J., Levine, A.S. Brain Res. (1998) [Pubmed]
  30. Hyperphagia and obesity in rats with bilateral ibotenic acid-induced lesions of the ventromedial hypothalamic nucleus. Shimizu, N., Oomura, Y., Plata-Salamán, C.R., Morimoto, M. Brain Res. (1987) [Pubmed]
  31. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Xu, B., Goulding, E.H., Zang, K., Cepoi, D., Cone, R.D., Jones, K.R., Tecott, L.H., Reichardt, L.F. Nat. Neurosci. (2003) [Pubmed]
  32. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Segal-Lieberman, G., Bradley, R.L., Kokkotou, E., Carlson, M., Trombly, D.J., Wang, X., Bates, S., Myers, M.G., Flier, J.S., Maratos-Flier, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  33. Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). Challis, B.G., Coll, A.P., Yeo, G.S., Pinnock, S.B., Dickson, S.L., Thresher, R.R., Dixon, J., Zahn, D., Rochford, J.J., White, A., Oliver, R.L., Millington, G., Aparicio, S.A., Colledge, W.H., Russ, A.P., Carlton, M.B., O'Rahilly, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  34. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Marsh, D.J., Weingarth, D.T., Novi, D.E., Chen, H.Y., Trumbauer, M.E., Chen, A.S., Guan, X.M., Jiang, M.M., Feng, Y., Camacho, R.E., Shen, Z., Frazier, E.G., Yu, H., Metzger, J.M., Kuca, S.J., Shearman, L.P., Gopal-Truter, S., MacNeil, D.J., Strack, A.M., MacIntyre, D.E., Van der Ploeg, L.H., Qian, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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