The regulation of food intake in mammalian hibernators: A review

Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology

Volumn 182, Issue 4, 2012, Pages 451-467

  Florant, Gregory L ^a   Healy, Jessica E ^b  

^a Department of Environmental and Radiological Health Sciences   (United States)

^b UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

AMPK; Arcuate nucleus; Food intake; Hibernation; Hypothalamus; Leptin; Torpor

Indexed keywords

GHRELIN; HYPOTHALAMUS HORMONE; INSULIN; LEPTIN;

ANIMAL; ANIMAL BEHAVIOR; BLOOD BRAIN BARRIER; CALORIC INTAKE; FOOD INTAKE; HIBERNATION; HYPOTHALAMUS; MAMMAL; METABOLISM; PERMEABILITY; PHYSIOLOGY; REVIEW; SEASON; SECRETION;

ANIMALS; APPETITE REGULATION; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; ENERGY INTAKE; GHRELIN; HIBERNATION; HYPOTHALAMIC HORMONES; HYPOTHALAMUS; INSULIN; LEPTIN; MAMMALS; PERMEABILITY; SEASONS;

ANIMALIA; MAMMALIA;

EID: 84859860277     PISSN: 01741578     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00360-011-0630-y     Document Type: Review

References (182)

1. Andrews MT, Squire TL, Bowen CM, Rollins MB (1998) Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal. Physiology 95: 8392-8397.
2. Andrews MT, Russeth KP, Drewes LR, Henry PG (2009) Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol Regul Integr Comp Physiol 296: R383-R393.
3. Ariyasu H, Takaya K, Hosoda H, Iwakura H, Ebihara K, Mori K (2002) Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. Endocrinology 143: 3341-3350.
4. Armitage KB, Shulenberger E (1972) Evidence for a circannual metabolic cycle in Citellus tridecemlineatus, a hibernator. Comp Biochem Physiol A Comp Physiol 42: 667-688.
5. Banks WA (2006) The blood-brain barrier as a regulatory interface in the gut-brain axes. Physiol Behav 89: 472-476.
6. Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, Morley JE (2004) Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53: 1253-1260.
7. Barazzoni R, Zanetti M, Stebel M, Biolo G, Cattin L, Guarnieri G (2003) Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats. Gastroenterology 124: 1188-1192.
8. Barger JL, Brand MD, Barnes BM, Boyer BB (2003) Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 284: R1306-R1313.
9. Barnes BM, Kretzmann M, Licht P, Zucker I (1986) The influence of hibernation on testis growth and spermatogenesis in the golden-mantled ground squirrel, Spermophilus lateralis. Biol Reprod 35: 1289-1297.
10. Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330: 1349-1354.
11. Bauman WA, Meryn S, Florant GL (1988) Cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the cerebral cortex of the non-hibernating and hibernating golden-mantled ground squirrel. Comp Biochem Physiol A Comp Physiol 91(1): 179-181.
12. Belgardt BF, Okamura T, Brüning JC (2009) Hormone and glucose signaling in POMC and AgRP neurons. J Physiol 587: 5305-5314.
13. Belsham DD, Cai F, Cui H, Smukler SR, Salapatek AM, Shkreta L (2004) Generation of a phenotypic array of hypothalamic neuronal cell models to study complex neuroendocrine disorders. Endocrinology 145: 393-400.
14. Bieber C, Ruf T (2009) Summer dormancy in edible dormice (Glis glis) without energetic constraints. Naturwissenschaften 96: 165-171.
15. Biggar KK, Storey KB (2011) The emerging roles of microRNAs in the molecular responses of metabolic rate depression. J Mol Cell Biol 3: 167-175.
16. Blazquez C, Woods A, de Ceballos ML, Carling D, Guzman M (1999) The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes. J Neurochem 73: 1674-1682.
17. Blouet C, Schwartz GJ (2010) Hypothalamic nutrient sensing in the control of energy homeostasis. Behav Brain Res 209: 1-12.
18. Boelen A, Wiersinga WM, Fliers E (2008) Fasting-induced changes in the hypothalamus-pituitary-thyroid axis. Thyroid 18: 123-129.
19. Boonstra R, Bradley AJ, Delehanty B (2011) Preparing for hibernation in ground squirrels: adrenal androgen production in summer linked to environmental severity in winter. Funct Ecol. doi: 10. 1111/j. 1365-2435. 2011. 01890. x.
20. Boswell T, Richardson RD, Schwartz MW, D'Alessio DA, Woods SC, Sipols AJ, Baskin DG, Kenagy GJ (1993) NPY and galanin in a hibernator: hypothalamic gene expression and effects on feeding. Brain Res Bull 32: 379-384.
21. Boswell T, Woods SC, Kenagy GJ (1994) Seasonal changes in body mass, insulin, and glucocorticoids of free-living golden-mantled ground squirrels. Gen Comp Endocrinol 96: 339-346.
22. Boyer BB, Ormseth OA, Buck L, Nicolson M, Pelleymounter MA, Barnes BM (1997) Leptin prevents posthibernation weight gain but does not reduce energy expenditure in Arctic GS. Comp Biochem Physiol 118: 405-412.
23. Bradbury M (1979) The concept of a blood-brain barrier. Wiley, New York.
24. Brand MD, Chien LF, Ainscow EK, Rolfe DFS, Porter RK (1994) The causes and functions of mitochondrial proton leak. Biochim Biophys Acta 1187: 132-139.
25. Büchner S, Stubbe M, Striese D (2003) Breeding and biological data for the common dormouse (Muscardinus avellanarius) in Eastern Saxony (Germany). Acta Zool Acad Sci Hung 49(Suppl. 1): 19-26.
26. Buck CL, Barnes BM (2000) Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator. Am J Physiol 279: R255-R262.
27. Buhr ED, Yoo SH, Takahashi JS (2010) Temperature as a universal resetting cue for mammalian circadian oscillators. Science 330: 379-385.
28. Buzadzic B, Spasic M, Saicic ZS, Radojicic R, Petrovic VM, Halliwell B (1990) Antioxidant defenses in the ground squirrel Citellus citellus. 2. The effect of hibernation. Free Radic Biol Med 9: 407-413.
29. Carling D (2005) AMP-activated protein kinase: balancing the scales. Biochimie 87: 87-91.
30. Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, van Der Ploeg LH, Howard AD, MacNeil DJ, Qian S (2004) Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y (NPY) and Agouti-related protein (AgRP). Endocrinol 145: 2607-2612.
31. Chen YJ, Wu CY, Shen JL, Chu SY, Chen CK, Chang YT, Chen CM (2008) Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome. Arch Dermatol 144: 1571-1575.
32. Chung D, Lloyd GP, Thomas RH, Guglielmo CG, Staples JF (2011) Mitochondrial respiration and succinate dehydrogenase are suppressed early during entrance into a hibernation bout, but membrane remodeling is only transient. J Comp Physiol B. doi: 10. 1007/s00360-010-0547-x.
33. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, Clements M, Al-Qassab H, Heffron H, Xu AW, Speakman JR, Barsh GS, Viollet B, Vaulont S, Ashford ML, Carling D, Withers DJ (2007) AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 117: 2325-2336.
34. Concannon P, Levac K, Rawson R, Tennant B, Bensadoun A (2001) Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks. Am J Physiol Regul Integr Comp Physiol 281: R951-R959.
35. Cota D, Proulx K, Blake Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ (2006) Hypothalamic mTOR signaling regulates food intake. Science 312: 927-930.
36. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411: 480-484.
37. Coyral-Castel S, Tosca L, Ferreira G, Jeanpierre E, Rame C, Lomet D, Caraty A, Monget P, Chabrolle C, Dupont J (2008) The effect of AMP-activated kinase activation on gonadotropin-releasing hormone secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats. J Neuroendocrinol 20: 335-346.
38. Cummings DE, Foster KE (2003) Ghrelin-leptin tango in body-weight regulation. Gastroenterology 124: 1532-1535.
39. Daan S, Barnes BM, Strijkstra AM (1991) Warming up for sleep?-Ground squirrels sleep during arousals from hibernation. Neurosci Lett 12: 265-268.
40. Dailey MJ, Bartness TJ (2010) Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding. Brain Res 1323: 94-108.
41. Dark J (2005) Annual lipid cycles in hibernators: integration of physiology and behavior. Annu Rev Nutr 25: 469-497.
42. Dark J, Miller DR (1997) Metabolic fuel privation in hibernating and awake ground squirrels. Physiol Behav 63: 59-65.
43. Davson H, Segal MB (1996) Special aspects of the blood-brain barrier. In: Physiology of the CSF and blood-brain barriers. CRC Press, Boca Raton, pp 303-485.
44. de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HA (2011) Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195.
45. de Souza FSJ, Nasif S, Lopez-Leal R, Levi DH, Low MJ, Rubinsten M (2011) The estrogen receptor ∝ colocalizes with proopiomelanocortin in hypothalamic neurons and binds to a conserved motif present in the neuron-specific enhancer nPE2. Eur J Pharmacol 660: 181-187.
46. Dhillon SS, Belsham DD (2011) Estrogen inhibits NPY secretion through membrane-associated estrogen receptor (ER)-α in clonal, immortalized hypothalamic neurons. Int J Obes 35: 198-207.
47. Diéguez C, Vazquez MJ, Romero A, López M, Nogueiras R (2011) Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins. Neuroendocrinology 94: 1-11.
48. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24: 31-55.
49. Edmond J (1992) Energy metabolism in developing brain cells. Can J Physiol Pharmacol 70: S118-S129.
50. Epperson LE, Karimpour-Fard A, Hunter LE, Martin SL (2011) Metabolic cycles in a circannual hibernator. Physiol Genomics 43: 799-807.
51. Farr SA, Banks WA, Morley JE (2006) Effects of leptin on memory processing. Peptides 27: 1420-1425.
52. Florant GL (1998) Lipid metabolism in hibernators: the importance of essential fatty acids. Am Zool 38: 331-340.
53. Florant GL, Baumann WA (1984) Seasonal variations in carbohydrate metabolism in mammalian hibernators: insulin and body weight changes. In: van Itallie TB, Hirsch J (eds) Advances in obesity research, vol 4. John Libbey, London, pp 57-64.
54. Florant GL, Lawrence AK, Williams K, Bauman WA (1985) Seasonal changes in pancreatic B-cell function in euthermic yellow-bellied marmots. Am J Physiol 249: R159-R165.
55. Florant GL, Nuttle LC, Mullinex DE, Rintoul DA (1990) Plasma and white adipose tissue lipid composition in marmots. Am J Physiol 258: R1123-R1131.
56. Florant GL, Singer L, Scheurink AJW, Park CR, Richardson RD, Woods SC (1991) Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period. Phys Behav 49: 335-338.
57. Florant GL, Hester L, Ameenuddin S, Rintoul DA (1993) The effect of a low essential fatty acid diet on hibernation in marmots. Am J Physiol 264: R747-R753.
58. Florant GL, Porst H, Peiffer A, Hudachek SF, Pittman C, Summers SA, Rajala MW, Scherer PE (2004) Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris). J Comp Physiol B 174: 633-639.
59. Florant GL, Fenn AM, Healy JE, Wilkerson GK, Handa RJ (2010) To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris). J Exp Bio 213: 2031-2037.
60. Fowler PA (1988) Seasonal endocrine cycles in the European hedgehog, Erinaceus europaeus. J Reprod Fert 84: 259-272.
61. Frank CL (1994) Polyunsaturate content and diet selection by ground squirrels (Spermophilus lateralis). Ecology 75: 458-463.
62. Frank CL, Dierenfeld ES, Storey KB (1998) The relationship between lipid peroxidation, hibernation, and food selection in mammals. Am Zool 38: 341-349.
63. Frank CL, Karpovich S, Barnes BM (2008) Dietary fatty acid composition and the hibernation patterns in free-ranging arctic ground squirrels. Physiol Biochem Zool 81: 486-495.
64. Freeman DA, Lewis DA, Kauffman AS, Blum RM, Dark J (2004) Reduced leptin concentrations are permissive for display of torpor in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 287: R97-R103.
65. Galster W, Morrison PR (1975) Gluconeogenesis in arctic ground squirrels between periods of hibernation. Am J Physiol 228: 325-330.
66. Gao Q, Horvath TL (2008) Cross-talk between estrogen and leptin signaling in the hypothalamus. Am J Physiol Endocrinol Metab 294: E817-E826.
67. Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL (2007) Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med 13: 89-94.
68. Geiser F (1988) Reduction of metabolism during hibernation and daily torpor in mammals and birds: temperature effect or physiological inhibition? J Comp Physiol B 158: 25.
69. Geiser F (1991) The effect of unsaturated and saturated dietary lipids on the pattern of daily torpor and the fatty acid composition of tissues and membranes of the deer mouse Peromyscus maniculatus. J Comp Physiol B 161: 590-597.
70. Geiser F (2004) Metabolic rate and body temperature reduction during hibernation and daily torpor. Ann Rev Physiol 66: 239-274.
71. Geiser F (2007) Yearlong hibernation in a marsupial mammal. Naturwissenschaften 94: 941-944.
72. Geiser F, Kenagy GJ (1987) Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator. Am J Physiol 252: R897-R901.
73. Geiser F, Kenagy GJ (1988) Duration of torpor bouts in relation to temperature and energy metabolism in hibernating ground squirrels. Physiol Zool 61: 442-449.
74. Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC (1996) Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci USA 93: 6231-6235.
75. Gluck EF, Stephens N, Swoap SJ (2006) Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway. Am J Physiol 291: R1303-R1309.
76. Hardie DG, Carling D (1997) The AMP-activated protein kinase-fuel gauge of the mammalian cell? Eur J Biochem 246: 259-273.
77. Hardie DG, Carling D, Sim ATR (1989) The AMP-activated protein kinase-a multisubstrate regulator of lipid metabolism. Trends Biochem Sci 14: 20-23.
78. Harlow HJ (1996) Winter body fat, food consumption and nonshivering thermogenesis of representative spontaneous and facultative hibernators: the white-tailed prairie dog and black-tailed prairie dog. J Therm Biol 22: 21-30.
79. Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827-829.
80. Healy JE, Richter MM, Suu L, Fried SK, Florant GL (2008) Changes in serum leptin concentrations with fat mass in golden-mantled ground squirrels (Spermophilus lateralis). In: Lovegrove BG, McKechnie AE (eds) Hypometabolism in animals: torpor, hibernation and cryobiology. University of KwaZulu-Natal, Pietermaritzburg.
81. Healy JE, Ostrom CE, Wilkerson GK, Florant GL (2010) Plasma ghrelin concentrations change with physiological state in a sciurid hibernator (Spermophilus lateralis). Gen Comp Endocrinol 166: 372-378.
82. Healy JE, Bateman JL, Ostrom CE, Florant GL (2011a) Peripheral ghrelin stimulates feeding behavior and positive energy balance in a sciurid hibernator. Horm Behav 59: 512-519.
83. Healy JE, Gearhart CN, Bateman JL, Handa RJ, Florant GL (2011b) AMPK and ACC change with fasting and physiological condition in euthermic and hibernating golden-mantled ground squirrels (Callospermophilus lateralis). Comp Biochem Physiol A Mol Integr Physiol 159: 322-331.
84. Heldmaier G, Ruf T (1992) Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162: 696.
85. Helgen KM, Cole FR, Helgen LE, Wilson DE (2009) Generic revision in the holarctic ground squirrel genus Spermophilus. J Mamm 90: 270-305.
86. Herwig A, Wilson D, Logie TJ, Boelen A, Morgan PJ, Mercer JG, Barrett P (2009) Photoperiod and acute energy deficits interact on components of the thyroid hormone system in hypothalamic tanycytes of the Siberian hamster. Am J Physiol Regul Integr Comp Physiol 296: R1307-R1315.
87. Hewson AK, Dickson SL (2000) Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J Neuroendocrinol 12: 1047-1049.
88. Hill VL, Florant GL (2000) The effect of a linseed oil diet on hibernation in yellow-bellied marmots (Marmota flaviventris). Physiol Behav 68: 431-437.
89. Ho PWL, Liu HF, Ho JWM, Zhang WY, Chu ACY, Kwok KHH, Ge X, Chan KH, Ramsden DB, Ho SL (2010) Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells. Neurotoxic Res 17: 332-343.
90. Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, James DE (2009) Insulin resistance is a cellular antioxidant defense mechanism. PNAS 106: 17787-17792.
91. Horman S, Hussain N, Dilworth SM, Storey KB, Rider MH (2005) Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation. Comp Biochem Physiol B Biochem Mol Biol 142: 374-382.
92. Hume ID, Beiglböck C, Ruf T, Frey-Roos F, Bruns U, Arnold W (2002) Seasonal changes in morphology and function of the gastrointestinal tract of free-living alpine marmots (Marmota marmota). J Comp Physiol B 172: 197-207.
93. Humphries MM, Thomas DW, Kramer DL (2003) The role of energy availability in mammalian hibernation: a cost-benefit approach. Physiol Biochem Zool 76: 165-179.
94. Jászberényi M, Bujdosó E, Bagosi Z, Telegdy G (2006) Mediation of the behavioral, endocrine and thermoregulatory actions of ghrelin. Horm Behav 50: 266-273.
95. Jinka TR, Tøien Ø, Drew JK (2011) Season primes the brain in an arctic hibernator to facilitate entrance into torpor mediated by adenosine A1 receptors. J Neurosci 31: 10752-10758.
96. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1: 15-25.
97. Karnani M, Burdakov D (2011) Multiple hypothalamic circuits sense and regulate glucose levels. Am J Physiol Regul Integr Comp Physiol 300: R47-R55.
98. Keen-Rhinehart E, Bartness TJ (2005) Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 288: R716-R722.
99. Kohno D, Sone H, Tanaka S, Kurita H, Gantulga D, Yada T (2011) AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats. Neurosci Lett 499: 194-198.
100. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660.
101. Kondo K (2007) Endogenous circannual clock and HP complex in a hibernation control system. Cold Spring Harbor Symp Quant Biol LXXIL: 607-613.
102. Kronfeld-Schor N, Richardson C, Silvia BA, Kunz TH, Widmaier EP (2000) Dissociation of leptin secretion and adiposity during prehibernatory fattening in little brown bats. Am J Physiol 279: R1277-R1281.
103. Kwok KH, Ho PW, Chu AC, Ho JW, Liu HF, Yiu DC, Chan KH, Kung MH, Ramsden DB, Ho SL (2010) Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity. Free Radic Biol Med 49: 1023-1035.
104. Lam TK (2011) Neuronal regulation of homeostasis by nutrient sensing. Nat Med 16: 392-395.
105. Lam TK, Schwartz GJ, Rossetti L (2005) Hypothalamic sensing of fatty acids. Nat Neurosci 8: 579-584.
106. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE (2009a) Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am J Physiol Regul Integr Comp Physiol 297: R655-R664.
107. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE (2009b) Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons. Am J Physiol Regul Integr Comp Physiol 297: R1351-R1357.
108. Levin BE (2002) Glucosensing neurons: the metabolic sensors of the brain? Diabetes Nutr Metab 15: 274-280.
109. Liu D, Chan SL, de Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, Mustafa K, de Cabo R, Mattson MP (2006) Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. Neuromolecular Med 8: 389-414.
110. Lopez M, Lage R, Saha AK, Perez-Tilve D, Vazquez MJ, Varela L, Sangiao-Alvarellos S, Tovar S, Raghay K, Rodríguez-Cuenca S, Deoliveira RM, Castaneda T, Datta R, Dong JZ, Culler M, Sleeman MW, Alvarez CV, Gallego R, Lelliott CJ, Carling D, Tschop MH, Dieguez C, Vidal-Puig A (2008) Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab 7: 389-399.
111. Lyman CP (1948) The oxygen consumption and temperature regulation of hibernating hamsters. J Exp Zool 109: 55-78.
112. Lyman CP, Willis JS, Malan A, Wang LCH (1982) Hibernation and torpor in mammals and birds. Academic Press, New York.
113. Malan A (2010) Is the torpor-arousal cycle of hibernation controlled by a non-temperature compensated circadian clock? J Biol Rhythm 25: 166-175.
114. Matheson AL, Campbell KL, Willis CKR (2010) Feeding, fasting and freezing: energetic effects of meal size and temperature on torpor expression by little brown bats Myotis lucifugus. J Exp Bio 213: 2165-2173.
115. Melnyk RB, Mrosovsky N, Martin JM (1983) Spontaneous obesity and weight loss: insulin binding and lipogenesis in the dormouse. Am J Physiol 245: R403-R407.
116. Melvin RG, Andrews MT (2009) Torpor induction in mammals: recent discoveries fueling new ideas. Trends Endocrinol Metab 20: 490-498.
117. Michener G (1993) Sexual differences in hibernaculum contents of Richardson's ground squirrels: males store food. In: Carey C, Florant GL, Wunder BA, Horwitz B (eds) Life in the cold: ecological, physiological, and molecular mechanisms. Westview Press, Colorado, p 575.
118. Migrenne S, Le Foll C, Levin BE, Magnan C (2011) Brain lipid sensing and nervous control of energy balance. Diabetes Metab 37: 83-88.
119. Millesi EHS, Dittami JP, Hoffmann LE, Daan S (1998) Parameters of mating effort and success in male European ground squirrels, Spermophilus citellus. Ethology 104: 298-313.
120. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Müller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415: 339-343.
121. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferré P, Birnbaum MJ, Stuck BJ, Kahn BB (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428: 569-574.
122. Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S (2008) Role of hypothalamic AMP-kinase in food intake regulation. Nutrition 24: 786-790.
123. Minor RK, Chang JW, de Cabo R (2009) Hungry for life: how the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction. Mol Cell Endocrinol 299: 79-88.
124. Mondal MS, Date Y, Yamaguchi H, Toshinai K, Tsuruta T, Kangawa K, Nakazato M (2005) Identification of ghrelin and its receptor in neurons of the rat arcuate nucleus. Regul Pept 126: 55-59.
125. Morton ML (1975) Seasonal cycles of body weights and lipid in Belding ground squirrels. Bull S C Acad Sci 74: 128-143.
126. Mountjoy PD, Rutter GA (2007) Glucose sensing by hypothalamic neurons and pancreatic islet cells: AMPle evidence for common mechanisms? Exp Physiol 92: 311-319.
127. Mouzannar R, McCafferty J, Benedetto G, Richardson C (2011) Transcriptional and phospho-proteomic screens reveal stem cell activation of insulin-resistance and transformation pathways following a single minimally toxic episode of ROS. Int J Genomics Proteomics 2: 34-49.
128. Mrosovsky N (1975) The amplitude and period of circannual cycles of body weight in golden-mantled ground squirrels with medial hypothalamic lesions. Brain Res 99: 97-116.
129. Mrosovsky N, Boshes M (1986) Meal patterns and food intakes of ground squirrels during circannual cycles. Appetite 7: 163-175.
130. Mrosovsky N, Powley TL (1977) Set points for body weight and fat. Behav Biol 20: 205-223.
131. Mrosovsky N, Sherry DF (1980) Animal anorexias. Science 207: 837-842.
132. Murphy M, Ebling FJ (2011) The role of hypothalamic tri-iodothyronine availability in seasonal regulation of energy balance and body weight. J Thyroid Res. doi: 10. 4061/2011/387562.
133. Nelson CJ, Otis JP, Carey HV (2010) Global analysis of circulating metabolites in hibernating ground squirrels. Comp Biochem Physiol Part D Genomics Proteomics 5: 265-273.
134. Nohara K, Zhang Y, Waraich RS, Laque A, Tiano JP, Tong J, Munzberg H, Mauvais-Jarvis F (2011) Early-life exposure to testosterone programs the hypothalamic melanocortin system. Endocrinology 152: 1661-1669.
135. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L (2002) Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51: 271-275.
136. Ormseth OA, Nicolson M, Pelleymounter MA, Boyer BB (1996) Leptin inhibits prehibernation hyperphagia and reduces body weight in arctic ground squirrels. Am J Physiol 271: R1775-R1779.
137. Orr AL, Lohse LA, Drew KL, Hermes-Lima M (2009) Physiological oxidative stress after arousal from hibernation in Arctic ground squirrel. Comp Biochem Physiol A Mol Integr Physiol 153: 213-221.
138. Ortmann S, Heldmaier G (2000) Regulation of body temperature and energy requirements of hibernating alpine marmots (Marmota marmota). Am J Physiol Regul Integr Comp Physiol 278: R698-R704.
139. Otis JP, Raybould HE, Carey HV (2011) Cholecystokinin activation of central satiety centers changes seasonally in a mammalian hibernator. Gen Comp Endocrinol 171: 269-274.
140. Panula P, Karlstedt K, Sallmen T, Peitsaro N, Kaslin J, Michelsen KA, Anichtchik O, Kukko-Lukjanov T, Lintunen M (2000) The histaminergic system in the brain: structural characteristics and changes in hibernation. J Chem Neuroanat 18: 65-74.
141. Parrilla R (1978) Flux of metabolic fuels during starvation in the rat. Pflugers Arch Eur J Physiol 374: 3-7.
142. Pelz KM, Routman D, Driscoll JR, Kriegsfeld LJ, Dark J (2008) Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 294: R255-R265.
143. Pengelley ET (1974) Circannual Clocks. Academic Press, San Francisco.
144. Pengelley ET, Asmundson SM (1969) Free-running periods of endogenous circannian rhythms in the golden-mantled ground squirrel, Citellus lateralis. Comp Biochem Physiol 30: 177-183.
145. Pengelley ET, Asmundson SJ, Barnes B, Aloia RC (1976) Relationship of light intensity and photoperiod to circannual rhythmicity in the hibernating ground squirrel, Citellus lateralis. Comp Biochem Physiol A Comp Physiol 53: 273-277.
146. Peruzzo B, Pastor FE, Blazquez JL, Schobitz K, Pelaez B, Amat P, Rodriguez EM (2000) A second look at the barriers of the medial basal hypothalamus. Exp Brain Res 132: 10-26.
147. Revel FG, Herwig A, Garidou ML, Dardente H, Menet JS, Masson-Pévet M, Simonneaux V, Saboureau M, Pévet P (2007) The circadian clock stops ticking during deep hibernation in the European hamster. Proc Natl Acad Sci USA 104: 13816-13820.
148. Roland AV, Moenter SM (2011) Glucosensing by GnRH neurons: inhibition by androgens and involvement of AMP-activated protein kinase. Mol Endocrinol 25: 847-858.
149. Ruf T, Arnold W (2008) Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis. Am J Physiol Regul Integr Comp Physiol 294: R1044-R1052.
150. Russell RL, O'Neill PH, Epperson LE, Martin SL (2010) Extensive use of torpor in 13-lined ground squirrels in the fall prior to cold exposure. J Comp Physiol B 180: 1165-1172.
151. Saleh J, Al-Wardy N, Farhan H, Al-Khanbashi M, Cianflone K (2011) Acylation stimulating protein: a female lipogenic factor? Obes Rev 12: 440-448.
152. Sallmén T, Beckman AL, Stanton TL, Eriksson KS, Tarhanen J, Tuomisto L, Panula P (1999) Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation. J Neurosci 19: 1824-1835.
153. Sallmén T, Lozada AF, Anichtchik OV, Beckman AL, Panula P (2003) Increased brain histamine H3 receptor expression during hibernation in golden-mantled ground squirrels. BMC Neurosci 4: 24.
154. Satinoff E (1967) Aberrations of regulation in ground squirrels following hypothalamic lesions. Am J Physiol 212: 215-220.
155. Satinoff E (1970) Hibernation and the Central Nervous System. Prog Physiol Psychol 3: 201-236.
156. Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, Scheurink A, Kahn SE, Baskin DG, Woods SC, Figlewicz DP (1992) Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 130: 3608-3616.
157. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404: 661-671.
158. Sheriff MJ, Kenagy GJ, Richter M, Lee T, Tøien Ø, Kohl F, Buck CL, Barnes BM (2011) Phenological variation in annual timing of hibernation and breeding in nearby populations of Arctic ground squirrels. Proc Biol Sci 278: 2369-2375.
159. Shimizu H, Arima H, Watanabe M, Goto M, Banno R, Sato I, Ozaki N, Nagasaki H, Oiso Y (2008) Glucocorticoids increase neuropeptide Y and agouti-related peptide gene expression via adenosine monophosphate-activated protein kinase signaling in the arcuate nucleus of rats. Endocrinol 149: 4544-4553.
160. Snapp BD, Heller HC (1981) Suppression of metabolism during hibernation in ground squirrels (Citellus lateralis). Physiol Zool 54: 297.
161. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897-916.
162. Speakman JR, Mitchell SE (2011) Caloric restriction. Mol Aspects Med. doi: 10. 1016/j. mam. 2011. 07. 001.
163. Storey KB, Storey JM (1990) Metabolic rate depression and biochemical adaptation in anaerobiosis, hibernation and estivation. Q Rev Biol 65: 145-174.
164. Storey KB, Storey JM (2010) Metabolic rate depression: the biochemistry of mammalian hibernation. Adv Clin Chem 52: 77-108.
165. Strauss A, Hoffmann IE, Walzl M, Millesi E (2009) Vaginal oestrus during the reproductive and non-reproductive period in European ground squirrels. Animal Reprod Sci 112: 362-370.
166. Szentirmai E, Kapas L, Krueger JM (2007) Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585.
167. Taché Y, Stengel A (2011) Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage. Curr Protein Pept Sci 12: 293-304.
168. Tartaglia LA (1997) The leptin receptor. J Biol Chem 272: 6093-6096.
169. Thorp CR, Ram PK, Florant GL (1994) Diet alters metabolic rate in the yellow-bellied marmot (Marmota flaviventris) during hibernation. Physiol Zool 67: 1213-1229.
170. Tøien Ø, Blake J, Edgar DM, Grahn DA, Heller HC, Barnes BM (2011) Hibernation in black bears: independence of metabolic suppression from body temperature. Science 331: 906-909.
171. Toshinai K, Mondal MS, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsukura S (2001) Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 281: 1220-1225.
172. Tschöp M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407: 908-913.
173. Verty ANA, Allen AM, Oldfield BJ (2010) The endogenous actions of hypothalamic peptides on brown adipose tissue thermogenesis in the rat. Endocrinol 151: 4236-4246.
174. Veyrat-Durebex C, Poher AL, Caillon A, Montet X, Rohner-Jeanrenaud F (2011) Alterations in lipid metabolism and thermogenesis with emergence of brown adipocytes in white adipose tissue in diet-induced obesity resistant Lou/C rats. Am J Physiol Endocrinol Metab 300: E1146-E1157.
175. Wade GN (1972) Gonadal hormones and behavioral regulation of body weight. Physiol Behav 8: 523-534.
176. Wang P, Walter RD, Bhat BG, Florant GL, Coleman RA (1997) Seasonal changes in enzymes of lipogenesis and triacylglycerol synthesis in the golden-mantled ground squirrel (Spermophilus lateralis). Comp Biochem Physiol B Biochem Mol Biol 118(2): 261-267.
177. Wang R, Cruciani-Guglielmacci C, Migrenne S, Magnan C, Cotero VE, Routh VH (2006) Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels. J Neurophysiol 95: 1491-1498.
178. Ward JM, Armitage KB (1981) Circannual rhythms of food consumption, body mass, and metabolism in yellow-bellied marmots. Comp Biochem Physiol A 69: 621-626.
179. Woods SC, Seeley RJ, Cota D (2008) Regulation of food intake through hypothalamic signaling networks involving mTOR. Annu Rev Nutr 28: 295-311.
180. Yan J, Barnes BM, Kohl F, Marr TG (2008) Modulation of gene expression in hibernating arctic ground squirrels. Physiol Genomics 32: 170-181.
181. Yang CS, Lam CKL, Chari M, Cheung GWC, Kokorovic A, Gao S, Leclerc I, Rutter GA, Lam TKT (2010) Hypothalamic AMP-activated protein kinase regulates glucose production. Diabetes 59: 2435-2443.
182. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-431.