Rapamycin ameliorates age-dependent obesity associated with increased mTOR signaling in hypothalamic POMC neurons

Neuron

Volumn 75, Issue 3, 2012, Pages 425-436

  Yang, Shi Bing ^a   Tien, An Chi ^a   Boddupalli, Gayatri ^a,c   Xu, Allison W ^b   Jan, Yuh Nung ^a   Jan, Lily Yeh ^a  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; AGOUTI RELATED PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; NEUROPEPTIDE Y; PROOPIOMELANOCORTIN; RAPAMYCIN; REGULATOR PROTEIN; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; UNCLASSIFIED DRUG;

AGE DISTRIBUTION; AGED; AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN NERVE CELL; CONTROLLED STUDY; DRUG MECHANISM; FOOD INTAKE; HYPOTHALAMUS; MOUSE; NERVE CELL EXCITABILITY; NERVE PROJECTION; NONHUMAN; OBESITY; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WEIGHT REDUCTION;

ACTION POTENTIALS; AGING; ANIMALS; EATING; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; KATP CHANNELS; MICE; MICE, TRANSGENIC; MULTIPLEX POLYMERASE CHAIN REACTION; NEURONS; NEUROTRANSMITTER AGENTS; OBESITY; ORGAN CULTURE TECHNIQUES; PATCH-CLAMP TECHNIQUES; PRO-OPIOMELANOCORTIN; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84864927001     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2012.03.043     Document Type: Article

References (67)

1. Ballanyi K. Protective role of neuronal KATP channels in brain hypoxia. J. Exp. Biol. 2004, 207:3201-3212.
2. Berglund E.D., Vianna C.R., Donato J., Kim M.H., Chuang J.C., Lee C.E., Lauzon D.A., Lin P., Brule L.J., Scott M.M., et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J. Clin. Invest. 2012, 122:1000-1009.
3. Berthoud H.R., Morrison C. The brain, appetite, and obesity. Annu. Rev. Psychol. 2008, 59:55-92.
4. Blagosklonny M.V. Hormesis does not make sense except in the light of TOR-driven aging. Aging 2011, 3:1051-1062.
5. Blagosklonny M.V. Rapamycin-induced glucose intolerance: Hunger or starvation diabetes. Cell Cycle 2011, 10:4217-4224.
6. Blouet C., Ono H., Schwartz G.J. Mediobasal hypothalamic p70 S6 kinase 1 modulates the control of energy homeostasis. Cell Metab. 2008, 8:459-467.
7. Bunel D.T., Delbende C., Blasquez C., Jégou S., Vaudry H. Effects of ions and ionic channel activators or blockers on release of alpha-MSH from perifused rat hypothalamic slices. Brain Res. Mol. Brain Res. 1990, 8:167-175.
8. Choi Y.J., Di Nardo A., Kramvis I., Meikle L., Kwiatkowski D.J., Sahin M., He X. Tuberous sclerosis complex proteins control axon formation. Genes Dev. 2008, 22:2485-2495.
9. Claret M., Smith M.A., Knauf C., Al-Qassab H., Woods A., Heslegrave A., Piipari K., Emmanuel J.J., Colom A., Valet P., et al. Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice. Diabetes 2011, 60:735-745.
10. Cota D., Proulx K., Smith K.A., Kozma S.C., Thomas G., Woods S.C., Seeley R.J. Hypothalamic mTOR signaling regulates food intake. Science 2006, 312:927-930.
11. Coupé B., Bouret S.G. Weighing on autophagy: a novel mechanism for the CNS regulation of energy balance. Cell Cycle 2012, 11:1477-1478.
12. Crane A., Aguilar-Bryan L. Assembly, maturation, and turnover of K(ATP) channel subunits. J. Biol. Chem. 2004, 279:9080-9090.
13. Diano S., Liu Z.W., Jeong J.K., Dietrich M.O., Ruan H.B., Kim E., Suyama S., Kelly K., Gyengesi E., Arbiser J.L., et al. Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat. Med. 2011, 17:1121-1127.
14. Dicken M.S., Tooker R.E., Hentges S.T. Regulation of GABA and glutamate release from proopiomelanocortin neuron terminals in intact hypothalamic networks. J. Neurosci. 2012, 32:4042-4048.
15. Elias C.F., Saper C.B., Maratos-Flier E., Tritos N.A., Lee C., Kelly J., Tatro J.B., Hoffman G.E., Ollmann M.M., Barsh G.S., et al. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comp. Neurol. 1998, 402:442-459.
16. Elmquist J.K. Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol. Behav. 2001, 74:703-708.
17. Forbes S., Bui S., Robinson B.R., Hochgeschwender U., Brennan M.B. Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway. Proc. Natl. Acad. Sci. USA 2001, 98:4233-4237.
18. Freedman D.S., Khan L.K., Serdula M.K., Galuska D.A., Dietz W.H. Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA 2002, 288:1758-1761.
19. Garelick M.G., Kennedy B.K. TOR on the brain. Exp. Gerontol. 2011, 46:155-163.
20. Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., Nadon N.L., Wilkinson J.E., Frenkel K., Carter C.S., et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009, 460:392-395.
21. Hill J.W., Elmquist J.K., Elias C.F. Hypothalamic pathways linking energy balance and reproduction. Am. J. Physiol. Endocrinol. Metab. 2008, 294:E827-E832.
22. Jaworski J., Spangler S., Seeburg D.P., Hoogenraad C.C., Sheng M. Control of dendritic arborization by the phosphoinositide-3'-kinase-Akt-mammalian target of rapamycin pathway. J. Neurosci. 2005, 25:11300-11312.
23. Keck T., Scheuss V., Jacobsen R.I., Wierenga C.J., Eysel U.T., Bonhoeffer T., Hübener M. Loss of sensory input causes rapid structural changes of inhibitory neurons in adult mouse visual cortex. Neuron 2011, 71:869-882.
24. Kishi M., Pan Y.A., Crump J.G., Sanes J.R. Mammalian SAD kinases are required for neuronal polarization. Science 2005, 307:929-932.
25. Kito H., Yamazaki D., Ohya S., Yamamura H., Asai K., Imaizumi Y. Up-regulation of K(ir)2.1 by ER stress facilitates cell death of brain capillary endothelial cells. Biochem. Biophys. Res. Commun. 2011, 411:293-298.
26. Knox S., Ge H., Dimitroff B.D., Ren Y., Howe K.A., Arsham A.M., Easterday M.C., Neufeld T.P., O'Connor M.B., Selleck S.B. Mechanisms of TSC-mediated control of synapse assembly and axon guidance. PLoS ONE 2007, 2:e375.
27. Koster J.C., Sha Q., Nichols C.G. Sulfonylurea and K(+)-channel opener sensitivity of K(ATP) channels. Functional coupling of Kir6.2 and SUR1 subunits. J. Gen. Physiol. 1999, 114:203-213.
28. Lee H.Y., Ge W.P., Huang W., He Y., Wang G.X., Rowson-Baldwin A., Smith S.J., Jan Y.N., Jan L.Y. Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. Neuron 2011, 72:630-642.
29. Li H., Matheny M., Tümer N., Scarpace P.J. Aging and fasting regulation of leptin and hypothalamic neuropeptide Y gene expression. Am. J. Physiol. 1998, 275:E405-E411.
30. Liss B., Bruns R., Roeper J. Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. EMBO J. 1999, 18:833-846.
31. Liu T., Kong D., Shah B.P., Ye C., Koda S., Saunders A., Ding J.B., Yang Z., Sabatini B.L., Lowell B.B. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 2012, 73:511-522.
32. Lyons D.J., Horjales-Araujo E., Broberger C. Synchronized network oscillations in rat tuberoinfundibular dopamine neurons: switch to tonic discharge by thyrotropin-releasing hormone. Neuron 2010, 65:217-229.
33. Ma D., Jan L.Y. ER transport signals and trafficking of potassium channels and receptors. Curr. Opin. Neurobiol. 2002, 12:287-292.
34. Ma D., Zerangue N., Lin Y.F., Collins A., Yu M., Jan Y.N., Jan L.Y. Role of ER export signals in controlling surface potassium channel numbers. Science 2001, 291:316-319.
35. Machado-Salas J.P., Scheibel A.B. Limbic system of the aged mouse. Exp. Neurol. 1979, 63:347-355.
36. Marcellini F., Giuli C., Papa R., Tirabassi G., Faloia E., Boscaro M., Polito A., Ciarapica D., Zaccaria M., Mocchegiani E. Obesity and body mass index (BMI) in relation to life-style and psycho-social aspects. Arch. Gerontol. Geriatr. 2009, 49(Suppl 1):195-206.
37. Meikle L., Pollizzi K., Egnor A., Kramvis I., Lane H., Sahin M., Kwiatkowski D.J. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J. Neurosci. 2008, 28:5422-5432.
38. Mokdad A.H., Bowman B.A., Ford E.S., Vinicor F., Marks J.S., Koplan J.P. The continuing epidemics of obesity and diabetes in the United States. JAMA 2001, 286:1195-1200.
39. Mori H., Inoki K., Münzberg H., Opland D., Faouzi M., Villanueva E.C., Ikenoue T., Kwiatkowski D., MacDougald O.A., Myers M.G., Guan K.L. Critical role for hypothalamic mTOR activity in energy balance. Cell Metab. 2009, 9:362-374.
40. Nakamura T.J., Nakamura W., Yamazaki S., Kudo T., Cutler T., Colwell C.S., Block G.D. Age-related decline in circadian output. J. Neurosci. 2011, 31:10201-10205.
41. Parton L.E., Ye C.P., Coppari R., Enriori P.J., Choi B., Zhang C.Y., Xu C., Vianna C.R., Balthasar N., Lee C.E., et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 2007, 449:228-232.
42. Pinto S., Roseberry A.G., Liu H., Diano S., Shanabrough M., Cai X., Friedman J.M., Horvath T.L. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004, 304:110-115.
43. Plum L., Ma X., Hampel B., Balthasar N., Coppari R., Münzberg H., Shanabrough M., Burdakov D., Rother E., Janoschek R., et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J. Clin. Invest. 2006, 116:1886-1901.
44. Price C.J., Samson W.K., Ferguson A.V. Nesfatin-1 inhibits NPY neurons in the arcuate nucleus. Brain Res. 2008, 1230:99-106.
45. Pocai A., Lam T.K., Gutierrez-Juarez R., Obici S., Schwartz G.J., Bryan J., Aguilar-Bryan L., Rossetti L. Hypothalamic K(ATP) channels control hepatic glucose production. Nature 2005, 434:1026-1031.
46. Raab-Graham K.F., Haddick P.C., Jan Y.N., Jan L.Y. Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites. Science 2006, 314:144-148.
47. Reed A.S., Unger E.K., Olofsson L.E., Piper M.L., Myers M.G., Xu A.W. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes 2010, 59:894-906.
48. Reiling J.H., Sabatini D.M. Stress and mTORture signaling. Oncogene 2006, 25:6373-6383.
49. Richard M.B., Taylor S.R., Greer C.A. Age-induced disruption of selective olfactory bulb synaptic circuits. Proc. Natl. Acad. Sci. USA 2010, 107:15613-15618.
50. Ropelle E.R., Pauli J.R., Fernandes M.F., Rocco S.A., Marin R.M., Morari J., Souza K.K., Dias M.M., Gomes-Marcondes M.C., Gontijo J.A., et al. A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss. Diabetes 2008, 57:594-605.
51. Ryu K.Y., Garza J.C., Lu X.Y., Barsh G.S., Kopito R.R. Hypothalamic neurodegeneration and adult-onset obesity in mice lacking the Ubb polyubiquitin gene. Proc. Natl. Acad. Sci. USA 2008, 105:4016-4021.
52. Sandoval D. CNS GLP-1 regulation of peripheral glucose homeostasis. Physiol. Behav. 2008, 94:670-674.
53. Sandoval D.A., Bagnol D., Woods S.C., D'Alessio D.A., Seeley R.J. Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake. Diabetes 2008, 57:2046-2054.
54. Schwappach B., Zerangue N., Jan Y.N., Jan L.Y. Molecular basis for K(ATP) assembly: transmembrane interactions mediate association of a K+ channel with an ABC transporter. Neuron 2000, 26:155-167.
55. Speier S., Yang S.B., Sroka K., Rose T., Rupnik M. KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP. Mol. Cell. Endocrinol. 2005, 230:51-58.
56. Sternson S.M., Shepherd G.M., Friedman J.M. Topographic mapping of VMH -> arcuate nucleus microcircuits and their reorganization by fasting. Nat. Neurosci. 2005, 8:1356-1363.
57. Vaisse C., Clement K., Guy-Grand B., Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 1998, 20:113-114.
58. van den Top M., Lyons D.J., Lee K., Coderre E., Renaud L.P., Spanswick D. Pharmacological and molecular characterization of ATP-sensitive K(+) conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus. Neuroscience 2007, 144:815-824.
59. Villanueva E.C., Münzberg H., Cota D., Leshan R.L., Kopp K., Ishida-Takahashi R., Jones J.C., Fingar D.C., Seeley R.J., Myers M.G. Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status. Endocrinology 2009, 150:4541-4551.
60. Wildonger J., Jan L.Y., Jan Y.N. The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels. Genes Dev. 2008, 22:2447-2453.
61. Williams K.W., Margatho L.O., Lee C.E., Choi M., Lee S., Scott M.M., Elias C.F., Elmquist J.K. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J. Neurosci. 2010, 30:2472-2479.
62. Wullschleger S., Loewith R., Hall M.N. TOR signaling in growth and metabolism. Cell 2006, 124:471-484.
63. Wyttenbach A., Hands S., King M.A., Lipkow K., Tolkovsky A.M. Amelioration of protein misfolding disease by rapamycin: translation or autophagy?. Autophagy 2008, 4:542-545.
64. Xu A.W., Kaelin C.B., Morton G.J., Ogimoto K., Stanhope K., Graham J., Baskin D.G., Havel P., Schwartz M.W., Barsh G.S. Effects of hypothalamic neurodegeneration on energy balance. PLoS Biol. 2005, 3:e415.
65. Yang S.B., Lee H.Y., Young D.M., Tien A.C., Rowson-Baldwin A., Shu Y.Y., Jan Y.N., Jan L.Y. Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J. Mol. Med. (Berl) 2012, 90:575-585.
66. Zerangue N., Schwappach B., Jan Y.N., Jan L.Y. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 1999, 22:537-548.
67. Zhang C., Zhu Q., Hua T. Aging of cerebellar Purkinje cells. Cell Tissue Res. 2010, 341:341-347.