Brain orexin promotes obesity resistance

Annals of the New York Academy of Sciences

Volumn 1264, Issue 1, 2012, Pages 72-86

  Kotz, Catherine ^a,b   Nixon, Joshua ^a,b   Butterick, Tammy ^a,b   Perez Leighton, Claudio ^a,b   Teske, Jennifer ^d,e   Billington, Charles ^a,c  

^a DEPARTMENT OF VETERANS AFFAIRS   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF ARIZONA   (United States)

^e Southern VA Healthcare System   (United States)

Author keywords

Energy expenditure; Nonexercise activity thermogenesis; Obesity; Orexin; Spontaneous physical activity

Indexed keywords

OREXIN; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR;

ARTICLE; CALORIC INTAKE; DISEASE RESISTANCE; ENERGY EXPENDITURE; HUMAN; NONHUMAN; OBESITY; PHYSICAL ACTIVITY; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; SLEEP PARAMETERS; SUPRACHIASMATIC NUCLEUS; THERMOGENESIS;

EID: 84864857152     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2012.06585.x     Document Type: Article

References (150)

1. Berthoud, H.R. & C. Morrison . 2008. The brain, appetite, and obesity. Annu. Rev. Psychol. 59: 55-92.
2. Must, A. et al . 1999. The disease burden associated with overweight and obesity. JAMA 282: 1523-1529.
3. Wang, Y. & T. Lobstein . 2006. Worldwide trends in childhood overweight and obesity. Int. J. Pediatr. Obes. 1: 11-25.
4. Ogden, C.L. et al . 2006. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 295: 1549-1555.
5. Flegal, K.M. et al . 2010. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 303: 235-241.
6. Bouchard, C. et al . 1990. The response to long-term overfeeding in identical twins. N. Engl. J. Med. 322: 1477-1482.
7. Forbes, G.B. et al . 1986. Deliberate overfeeding in women and men: energy cost and composition of the weight gain. Br. J. Nutr. 56: 1-9.
8. Mustelin, L. et al . 2009. Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins. Int. J. Obes. 33: 29-36.
9. Hamilton, M.T., D.G. Hamilton & T.W. Zderic . 2007. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 56: 2655-2667.
10. Levine, J.A. 2002. Non-exercise activity thermogenesis (NEAT). Best Pract. Res. Clin. Endocrinol. Metab. 16: 679-702.
11. Levine, J.A., N.L. Eberhardt & M.D. Jensen . 1999. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 283: 212-214.
12. Levine, J.A. et al . 2005. Interindividual variation in posture allocation: possible role in human obesity. Science 307: 584-586.
13. Fruhbeck, G. 2005. Does a NEAT difference in energy expenditure lead to obesity? Lancet 366: 615-616.
14. Ravussin, E. 2005. Physiology. A NEAT way to control weight? Science 307: 530-531.
15. Snitker, S., P.A. Tataranni & E. Ravussin . 2001. Spontaneous physical activity in a respiratory chamber is correlated to habitual physical activity. Int. J. Obes. Relat. Metab. Disord. 25: 1481-1486.
16. Kotz, C.M. et al . 2006. Orexin A mediation of time spent moving in rats: neural mechanisms. Neuroscience 142: 29-36.
17. Garland, T., Jr. et al . 2011. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives. J. Exp. Biol. 214: 206-229.
18. Dishman, R.K. 2008. Gene-physical activity interactions in the etiology of obesity: behavioral considerations. Obesity 16 Suppl 3: S60-S65.
19. Teske, J.A., C.J. Billington & C.M. Kotz . 2008. Neuropeptidergic mediators of spontaneous physical activity and non-exercise activity thermogenesis. Neuroendocrinology 87: 71-90.
20. Sakurai, T. et al . 1998. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92: 573-585.
21. de Lecea, L. et al . 1998. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. USA 95: 322-327.
22. Burdakov, D., O. Gerasimenko & A. Verkhratsky . 2005. Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J. Neurosci. 25: 2429-2433.
23. Li, Y. et al . 2002. Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 36: 1169-1181.
24. Schone, C. et al . 2011. Dichotomous cellular properties of mouse orexin/hypocretin neurons. J. Physiol. 589: 2767-2779.
25. Ammoun, S. et al . 2003. Distinct recognition of OX1 and OX2 receptors by orexin peptides. J. Pharmacol. Exp. Ther. 305: 507-514.
26. Yang, B. & A.V. Ferguson . 2003. Orexin-A depolarizes nucleus tractus solitarius neurons through effects on nonselective cationic and K+ conductances. J. Neurophysiol. 89: 2167-2175.
27. van den Pol, A.N. et al. 1998. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J. Neurosci. 18: 7962-7971.
28. Larsson, K.P. et al . 2005. Orexin-A-induced Ca2+ entry: evidence for involvement of trpc channels and protein kinase C regulation. J. Biol. Chem. 280: 1771-1781.
29. Uramura, K. et al . 2001. Orexin-a activates phospholipase C- and protein kinase C-mediated Ca2 +signaling in dopamine neurons of the ventral tegmental area. Neuroreport 12: 1885-1889.
30. Follwell, M.J. & A.V. Ferguson . 2002. Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus. J. Physiol. 545: 855-867.
31. Kiwaki, K. et al . 2004. Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats. Am. J. Physiol. Endocrinol. Metab. 286: E551-559.
32. Kotz, C.M. et al . 2002. Feeding and activity induced by orexin A in the lateral hypothalamus in rats. Regul. Pept. 104: 27-32.
33. Novak, C.M., C.M. Kotz & J.A. Levine . 2006. Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats. Am. J. Physiol. Endocrinol. Metab. 290: E396-403.
34. Teske, J.A. et al . 2006. Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291: R889-899.
35. Date, Y. et al . 1999. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc. Natl. Acad. Sci. USA 96: 748-753.
36. Mintz, E.M. et al . 2001. Distribution of hypocretin-(orexin) immunoreactivity in the central nervous system of Syrian hamsters (Mesocricetus auratus). J. Chem. Neuroanat. 21: 225-238.
37. Moore, R.Y., E.A. Abrahamson & A. Van Den Pol . 2001. The hypocretin neuron system: an arousal system in the human brain. Arch. Ital. Biol. 139: 195-205.
38. Nixon, J.P. & L. Smale . 2007. A comparative analysis of the distribution of immunoreactive orexin A and B in the brains of nocturnal and diurnal rodents. Behav. Brain Funct. 3: 28.
39. Peyron, C. et al . 1998. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18: 9996-10015.
40. Espana, R.A. et al . 2005. Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal-related structures. J. Comp. Neurol. 481: 160-178.
41. Ciriello, J. et al . 2003. Identification of neurons containing orexin-B (hypocretin-2) immunoreactivity in limbic structures. Brain Res. 967: 123-131.
42. Krout, K.E., T.C. Mettenleiter & A.D. Loewy . 2003. Single CNS neurons link both central motor and cardiosympathetic systems: a double-virus tracing study. Neuroscience 118: 853-866.
43. Geerling, J.C., T.C. Mettenleiter & A.D. Loewy . 2003. Orexin neurons project to diverse sympathetic outflow systems. Neuroscience 122: 541-550.
44. Oldfield, B.J. et al . 2007. Lateral hypothalamic 'command neurons' with axonal projections to regions involved in both feeding and thermogenesis. Eur. J. Neurosci. 25: 2404-2412.
45. Cluderay, J.E., D.C. Harrison & G.J. Hervieu . 2002. Protein distribution of the orexin-2 receptor in the rat central nervous system. Regul. Pept. 104: 131-144.
46. Greco, M.A. & P.J. Shiromani . 2001. Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats. Brain Res. Mol. Brain Res. 88: 176-182.
47. Hervieu, G.J. et al . 2001. Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience 103: 777-797.
48. Marcus, J.N. et al . 2001. Differential expression of orexin receptors 1 and 2 in the rat brain. J. Comp. Neurol. 435: 6-25.
49. Sunter, D. et al . 2001. Orexins: effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem. Brain Res. 907: 27-34.
50. Trivedi, P. et al . 1998. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 438: 71-75.
51. Berridge, C.W., R.A. Espana & N.M. Vittoz . 2010. Hypocretin/orexin in arousal and stress. Brain Res. 1314: 91-102.
52. Harris, G.C. & G. Aston-Jones . 2006. Arousal and reward: a dichotomy in orexin function. Trends Neurosci. 29: 571-577.
53. Kotz, C.M. 2006. Integration of feeding and spontaneous physical activity: role for orexin. Physiol. Behav. 88: 294-301.
54. Sakurai, T. 2005. Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med. Rev. 9: 231-241.
55. Sharf, R., M. Sarhan & R.J. Dileone . 2010. Role of orexin/hypocretin in dependence and addiction. Brain Res. 1314: 130-138.
56. Tsujino, N. & T. Sakurai . 2009. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol. Rev. 61: 162-176.
57. Hara, J. et al . 2001. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30: 345-354.
58. Akiyama, M. et al . 2004. Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice. Eur. J. Neurosci. 20: 3054-3062.
59. Mieda, M. et al . 2004. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc. Natl. Acad. Sci. USA 101: 4649-4654.
60. Funato, H. et al . 2009. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 9: 64-76.
61. Ammoun, S. et al . 2006. OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms: the role of Ca2+ influx in OX1 receptor signaling. Mol. Endocrinol. 20: 80-99.
62. Ekholm, M.E., L. Johansson & J.P. Kukkonen . 2007. IP3-independent signalling of OX1 orexin/hypocretin receptors to Ca2+ influx and ERK. Biochem. Biophys. Res. Commun. 353: 475-480.
63. Johansson, L., M.E. Ekholm & J.P. Kukkonen . 2007. Regulation of OX1 orexin/hypocretin receptor-coupling to phospholipase C by Ca2 +influx. Br. J. Pharmacol. 150: 97-104.
64. Johansson, L., M.E. Ekholm & J.P. Kukkonen . 2008. Multiple phospholipase activation by OX(1) orexin/hypocretin receptors. Cell Mol. Life Sci. 65: 1948-1956.
65. Kukkonen, J.P. & K.E. Akerman . 2001. Orexin receptors couple to Ca2+ channels different from store-operated Ca2+ channels. Neuroreport 12: 2017-2020.
66. Lund, P.E. et al . 2000. The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C. J. Biol. Chem. 275: 30806-30812.
67. Magga, J. et al . 2006. Agonist potency differentiates G protein activation and Ca2+ signalling by the orexin receptor type 1. Biochem. Pharmacol. 71: 827-836.
68. Nasman, J. et al . 2006. The orexin OX1 receptor regulates Ca2+ entry via diacylglycerol-activated channels in differentiated neuroblastoma cells. J. Neurosci. 26: 10658-10666.
69. Peltonen, H.M. et al . 2009. Involvement of TRPC3 channels in calcium oscillations mediated by OX(1) orexin receptors. Biochem. Biophys. Res. Commun. 385: 408-412.
70. Tang, J. et al . 2008. The signalling profile of recombinant human orexin-2 receptor. Cell Signal. 20: 1651-1661.
71. Hoang, Q.V. et al . 2003. Effects of orexin (hypocretin) on GIRK channels. J. Neurophysiol. 90: 693-702.
72. Hoang, Q.V. et al . 2004. Orexin (hypocretin) effects on constitutively active inward rectifier K +channels in cultured nucleus basalis neurons. J. Neurophysiol. 92: 3183-3191.
73. Mukai, K. et al . 2009. Electrophysiological effects of orexin/hypocretin on nucleus accumbens shell neurons in rats: an in vitro study. Peptides 30: 1487-1496.
74. van den Pol, A.N. et al . 2002. Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP-expressing locus coeruleus. J. Physiol. 541: 169-185.
75. Samson, W.K. et al . 2002. Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates. Regul. Pept. 104: 97-103.
76. Burlet, S., C.J. Tyler & C.S. Leonard . 2002. Direct and indirect excitation of laterodorsal tegmental neurons by Hypocretin/Orexin peptides: implications for wakefulness and narcolepsy. J. Neurosci. 22: 2862-2872.
77. Bayer, L. et al . 2002. Selective action of orexin (hypocretin) on nonspecific thalamocortical projection neurons. J. Neurosci. 22: 7835-7839.
78. Bisetti, A. et al . 2006. Excitatory action of hypocretin/orexin on neurons of the central medial amygdala. Neuroscience 142: 999-1004.
79. Liu, R.J., A. N. van den Pol & G.K. Aghajanian . 2002. Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. J. Neurosci. 22: 9453-9464.
80. Burdakov, D., B. Liss & F.M. Ashcroft . 2003. Orexin excites GABAergic neurons of the arcuate nucleus by activating the sodium-calcium exchanger. J. Neurosci. 23: 4951-4957.
81. Kohlmeier, K.A., T. Inoue & C.S. Leonard . 2004. Hypocretin/orexin peptide signaling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum. J. Neurophysiol. 92: 221-235.
82. Wenzel, J. et al . 2009. Hypocretin/orexin increases the expression of steroidogenic enzymes in human adrenocortical NCI H295R cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297: R1601-R1609.
83. Karteris, E. et al . 2005. Food deprivation differentially modulates orexin receptor expression and signaling in rat hypothalamus and adrenal cortex. Am. J. Physiol. Endocrinol. Metab. 288: E1089-E1100.
84. Levin, B.E., S. Hogan & A.C. Sullivan . 1989. Initiation and perpetuation of obesity and obesity resistance in rats. Am. J. Physiol. 256: R766-R771.
85. Ricci, M.R. & B.E. Levin . 2003. Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285: R610-R618.
86. Levin, B.E. et al . 1997. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am.J. Physiol. 273: R725-R730.
87. Levin, B.E. & A.A. Dunn-Meynell . 2002. Reduced central leptin sensitivity in rats with diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283: R941-R948.
88. Clegg, D.J. et al . 2005. Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am. J. Physiol. Regul. Integr Comp. Physiol. 288: R981-R986.
89. Thorpe, A.J. & C.M. Kotz . 2005. Orexin A in the nucleus accumbens stimulates feeding and locomotor activity. Brain Res. 1050: 156-162.
90. Teske, J.A., C.J. Billington, M.A. Kuskowksi, & C.M. Kotz 2012. Spontaneous physical activity protects against fat mass gain. Int. J. Obes. (Lond). 36(4): 603-613. doi:10.1038/ijo.2011.108.
91. Levin, B.E. 1991. Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat. Physiol. Behav. 50: 573-581.
92. Kotz, C.M., J.A. Teske & C.J. Billington . 2008. Neuroregulation of nonexercise activity thermogenesis and obesity resistance. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294: R699-710.
93. Teske, J.A., C.J. Billington & C.M. Kotz . 2010. Hypocretin/orexin and energy expenditure. Acta Physiol. (Oxf). 198: 303-312.
94. Sweet, D.C. et al . 1999. Feeding response to central orexins. Brain Res. 821: 535-538.
95. Thorpe, A.J. et al . 2003. Peptides that regulate food intake: regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284: R1409-1417.
96. Teske, J.A. & C.M. Kotz . 2009. Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297: R176-184.
97. Novak, C.M., M. Zhang & J.A. Levine . 2007. Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity. Brain Res. 1169: 57-68.
98. Novak, C.M. & J.A. Levine . 2009. Daily intraparaventricular orexin-A treatment induces weight loss in rats. Obesity 17: 1493-1498.
99. Mavanji, V. et al . 2010. Elevated sleep quality and orexin receptor mRNA in obesity-resistant rats. Int. J. Obes 34: 1576-1588.
100. Feder, M.E. et al . 2010. Locomotion in response to shifting climate zones: not so fast. Annu. Rev. Physiol. 72: 167-190.
101. Novak, C.M. et al . 2010. Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity. Hormo. Behav. 58: 355-367.
102. Novak, C.M. et al . 2009. Endurance capacity, not body size, determines physical activity levels: role of skeletal muscle PEPCK. PloS ONE 4: e5869.
103. Britton, S.L. & L.G. Koch . 2001. Animal genetic models for complex traits of physical capacity. Exe. Sport Sci. Rev. 29: 7-14.
104. Hagan, J.J. et al . 1999. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc. Natl. Acad. Sci. USA 96: 10911-10916.
105. Horvath, T.L. et al . 1999. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J. Comp. Neurol. 415: 145-159.
106. Bourgin, P. et al . 2000. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J. Neurosci. 20: 7760-7765.
107. Methippara, M.M. et al . 2000. Effects of lateral preoptic area application of orexin-A on sleep-wakefulness. Neuroreport 11: 3423-3426.
108. Adamantidis, A.R. et al . 2007. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450: 420-424.
109. Weaver, D.R. 1998. The suprachiasmatic nucleus: a 25-year retrospective. J. Biol. Rhythms 13: 100-112.
110. Abrahamson, E.E., R.K. Leak & R.Y. Moore . 2001. The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12: 435-440.
111. Deurveilher, S. & K. Semba . 2005. Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state. Neuroscience 130: 165-183.
112. Yoshida, K. et al . 2006. Afferents to the orexin neurons of the rat brain. J. Comp. Neurol. 494: 845-861.
113. Martinez, G.S., L. Smale & A.A. Nunez . 2002. Diurnal and nocturnal rodents show rhythms in orexinergic neurons. Brain Res. 955: 1-7.
114. Zhang, S. et al . 2004. Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep 27: 619-627.
115. Chemelli, R.M. et al . 1999. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98: 437-451.
116. Estabrooke, I.V. et al . 2001. Fos expression in orexin neurons varies with behavioral state. J. Neurosci. 21: 1656-1662.
117. Nixon, J.P. & L. Smale . 2004. Individual differences in wheel-running rhythms are related to temporal and spatial patterns of activation of orexin A and B cells in a diurnal rodent (Arvicanthis niloticus). Neuroscience 127: 25-34.
118. Tsunematsu, T. et al . 2011. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J. Neurosci. 31: 10529-10539.
119. Ida, T. et al . 1999. Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Res. 821: 526-529.
120. Yamanaka, A. et al . 2003. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38: 701-713.
121. Wu, M.F. et al . 2002. Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283: R1079-1086.
122. Overeem, S. et al . 2001. Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. J. Clin. Neurophysiol. 18: 78-105.
123. Siegel, J.M. 2004. Hypocretin (orexin): role in normal behavior and neuropathology. Annu. Rev. Psychol. 55: 125-148.
124. Kiyashchenko, L.I. et al . 2002. Release of hypocretin (orexin) during waking and sleep states. J. Neurosci. 22: 5282-5286.
125. Schuld, A. et al . 2000. Increased body-mass index in patients with narcolepsy. Lancet 355: 1274-1275.
126. Middelkoop, H.A. et al . 1995. Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring. Psychophysiology 32: 286-291.
127. Stamatakis, K.A. & N.M. Punjabi . 2010. Effects of sleep fragmentation on glucose metabolism in normal subjects. Chest 137: 95-101.
128. Spiegel, K. et al . 2004. Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann. Intern. Med. 141: 846-850.
129. Blanchong, J.A. et al . 1999. Nocturnal and diurnal rhythms in the unstriped Nile rat, Arvicanthis niloticus. J. Biol. Rhythms 14: 364-377.
130. Schwartz, M.D. & L. Smale . 2005. Individual differences in rhythms of behavioral sleep and its neural substrates in Nile grass rats. J. Biol. Rhythms 20: 526-537.
131. Donahoo, W.T., J.A. Levine & E.L. Melanson . 2004. Variability in energy expenditure and its components. Curr. Opin. Clin. Nutr. Metab. Care 7: 599-605.
132. Widdowson, E.M., O.G. Edholm & C.R. Mc . 1954. The food intake and energy expenditure of cadets in training. Br. J. Nutr. 8: 147-155.
133. Zurlo, F. et al . 1992. Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians. Am. J. Physiol. 263: E296-E300.
134. Tou, J.C. & C.E. Wade . 2002. Determinants affecting physical activity levels in animal models. Exp. Biol. Med. 227: 587-600.
135. Hill, J.O. 2009. Can a small-changes approach help address the obesity epidemic? A report of the Joint Task Force of the American Society for Nutrition, Institute of Food Technologists, and International Food Information Council. Am. J. Clin. Nutr. 89: 477-484.
136. Leibel, R.L., M. Rosenbaum & J. Hirsch . 1995. Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med. 332: 621-628.
137. Berthoud, H.R. & H. Munzberg . 2011. The lateral hypothalamus as integrator of metabolic and environmental needs: from electrical self-stimulation to opto-genetics. Physiol. Behav. 104: 29-39.
138. Sakurai, T. et al . 2005. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron 46: 297-308.
139. Kampe, J. et al . 2009. An anatomic basis for the communication of hypothalamic, cortical and mesolimbic circuitry in the regulation of energy balance. Eur. J. Neurosci. 30: 415-430.
140. Burt, J. et al . 2011. Local network regulation of orexin neurons in the lateral hypothalamus. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301: R572-R580.
141. Eggermann, E. et al . 2003. The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization. J. Neurosci. 23: 1557-1562.
142. Winsky-Sommerer, R. et al . 2004. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J. Neurosci. 24: 11439-11448.
143. Williams, R.H. et al . 2008. Adaptive sugar sensors in hypothalamic feeding circuits. Proc. Natl. Acad. Sci. USA 105: 11975-11980.
144. Moriguchi, T. et al . 1999. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neurosci. Lett. 264: 101-104.
145. Cai, X.J. et al . 1999. Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 48: 2132-2137.
146. Silva, J.P. et al . 2009. Regulation of adaptive behaviour during fasting by hypothalamic Foxa2. Nature 462: 646-650.
147. Louis, G.W. et al . 2010. Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons. J. Neurosci. 30: 11278-11287.
148. Karnani, M.M. et al . 2011. Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron 72: 616-629.
149. Acuna-Goycolea, C. & A. van den Pol . 2004. Glucagon-like peptide 1 excites hypocretin/orexin neurons by direct and indirect mechanisms: implications for viscera-mediated arousal. J. Neurosci. 24: 8141-8152.
150. Malisch, J.L. et al . 2009. Behavioral despair and home-cage activity in mice with chronically elevated baseline corticosterone concentrations. Behav. Genet. 39: 192-201.