Comprehensive Physiology Wiley Online Library

Metabolic Flexibility: Hibernation, Torpor, and Estivation

Full Article on Wiley Online Library



ABSTRACT

Many environmental conditions can constrain the ability of animals to obtain sufficient food energy, or transform that food energy into useful chemical forms. To survive extended periods under such conditions animals must suppress metabolic rate to conserve energy, water, or oxygen. Amongst small endotherms, this metabolic suppression is accompanied by and, in some cases, facilitated by a decrease in core body temperature—hibernation or daily torpor—though significant metabolic suppression can be achieved even with only modest cooling. Within some ectotherms, winter metabolic suppression exceeds the passive effects of cooling. During dry seasons, estivating ectotherms can reduce metabolism without changes in body temperature, conserving energy reserves, and reducing gas exchange and its inevitable loss of water vapor. This overview explores the similarities and differences of metabolic suppression among these states within adult animals (excluding developmental diapause), and integrates levels of organization from the whole animal to the genome, where possible. Several similarities among these states are highlighted, including patterns and regulation of metabolic balance, fuel use, and mitochondrial metabolism. Differences among models are also apparent, particularly in whether the metabolic suppression is intrinsic to the tissue or depends on the whole‐animal response. While in these hypometabolic states, tissues from many animals are tolerant of hypoxia/anoxia, ischemia/reperfusion, and disuse. These natural models may, therefore, serve as valuable and instructive models for biomedical research. © 2016 American Physiological Society. Compr Physiol 6:737‐7771, 2016.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. The effect of ambient (environmental) temperature on the metabolic rate of a typical nontorpid endotherm (e.g., a small eutherian mammal; red line) and an ectotherm vertebrate (blue line) of similar mass. Between 27 and 36°C (the Thermal Neutral Zone [TNZ], bounded by dashed lines) the endotherm metabolic rate is minimal, and T b is maintained near 37°C by regulating heat loss, for example, through alterations in piloerection and peripheral blood flow. Below 27°C, the endotherm must increase thermogenesis, that is, increases in metabolism solely for the sake of producing more heat (e.g., shivering, activation of BAT) to defend T b. The T b of the ectotherm is very close to the ambient temperature and metabolism is regulated largely by passive thermal effects on enzyme‐catalyzed reactions. Note the different scales on the two axes. For more details, consult ref. .
Figure 2. Figure 2. The ETS of a typical animal. The enzyme complexes are associated with the inner mitochondrial membrane (IMM). NADH, derived from the Krebs cycle, is oxidized by complex I and succinate by complex II. Electrons from these substrates are transferred to the mobile carrier coenzyme Q (Q), which transfers them to complex III, and subsequently to complex IV via cytochrome C (C). Approximately 40% of free energy released by substrate oxidation is used by complexes I, III, and IV to pump protons from the matrix to the intermembrane space (IMS), between the IMM and the outer mitochondrial membrane (OMM). The remainder of the free energy is released as heat. In the presence of ADP, derived from ATPase‐catalyzed ATP hydrolysis, protons return to the matrix, powering ATP synthesis by complex V. The IMM of eutherian mammal BAT contain little complex V but, uniquely, significant amounts of UCP1. When BAT adipocytes are activated by sympathetic nervous stimulation, protons flow from the IMS to the matrix through UCP1, stimulating ETS substrate oxidation and heat production, but no ATP synthesis.
Figure 3. Figure 3. Phylogenetic tree showing mammalian orders with species that use hibernation (H) or torpor (T). Modified with permission from ref. .
Figure 4. Figure 4. Avian phylogenetic tree showing families with species where adults display torpor (T) or possible hibernation (H?). Modified with permission from ref. .
Figure 5. Figure 5. Body composition of young‐of‐the‐year thirteen‐lined ground squirrels. Shortly after weaning animals were weighed and body composition was determined using quantitative H+ nuclear magnetic resonance. See ref. for experimental details. Values are means ± standard error of three males and four females from the same litter. J.F. Staples, D.J. Chung, and C.G. Guglielmo, unpublished data.
Figure 6. Figure 6. The effect of food quantity and PUFA content on hibernation in eastern chipmunks (Tamias striatus). Animals were fed either on natural forage (Control) or had their diet supplemented with food that had a similar PUFA content to the natural diet (Natural PUFA) or with food containing higher PUFA than the natural diet (High PUFA). Data from ref. with permission.
Figure 7. Figure 7. Fasting induced daily torpor in mice (Mus musculus). Body temperature T b of two individual Balb/c mice over the course of a week during which fasting occurred. Photophase began at 9 pm, and scotophase (black bars) began at 9 am. Fasting began just prior to the start of the scotophase on Monday (7 am) and ended 3 days later. Prior to fasting, mice maintained a fairly constant T b and torpor was not observed. Once fasting began, T b became more variable, and bouts of daily torpor occurred, where T b dropped below 31°C (indicated by dashed line). These mice underwent one or more bouts of daily torpor on each of the 3 days of fasting. Once food was returned, T b stabilized near 37°C, and no bouts of torpor were observed. Modified from ref. with permission.
Figure 8. Figure 8. Core body temperature of a thirteen lined ground squirrel through several torpor bouts at the beginning of the hibernation season (A). Metabolic rate and body temperature of a ground squirrel in the different stages of a torpor bout (B). Modified from ref. with permission.
Figure 9. Figure 9. Body temperature and metabolic rate of a Djungarian hamster showing a spontaneous bout of daily torpor. Modified from ref. with permission.
Figure 10. Figure 10. (A) Activity of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) in different phases of hibernation bout in Syrian hamsters. “Summer” and “Winter” animals were euthermic (T b ∼ 37°C). “IBA” = interbout arousal (equivalent to IBE), “cooling” = entrance. Groups differing significantly (p < 0.01, Tukey's post‐hoc comparisons) are denoted by different superscripts. (B) The effect of cardiac sarcoplasmic reticulum phospholipid fatty acid composition on Ca2+ ATPase activity in different phases of a hibernation bout. Ca2+ ATPase activity as a function of the proportions (% of total fatty acids) linoleic acid (LA 18:2, n‐6) (a), docosahexaenoic acid (DHA 22:6, n‐3) (b), and (c) the ratio of LA/DHA. Black dots indicate data from torpid animals, black triangles from cooling animals, grey dots from animals during interbout arousals, and open dots from nonhibernating summer and winter Syrian hamsters. Modified from ref. .
Figure 11. Figure 11. (A) The content of cytochrome a in liver mitochondria isolated from Ictidomys tridecemlineatus does not differ significantly between torpor and IBE. (B) State 3 respiration (with 10 mmol/L succinate as substrate plus 1 μmol/L rotenone and 0.2 mmol/L ADP) of liver mitochondria isolated from torpid ground squirrels is suppressed by approximately 65% whether expressed relative to mitochondrial protein or cytochrome a content. Asterisk indicates significant difference (p < 0.05, t test). K. Mathers, R. Balaban, J. Staples, unpublished data.
Figure 12. Figure 12. The effect of in vitro assay temperature on the respiration of liver mitochondria isolated from a hibernator, Ictidomys tridecemlineatus. At 37 and 25°C, state 3 respiration (in the presence of 10 mmol/L succinate, 1 μmol/L rotenone, and 0.2 mmol/L ADP) is significantly higher when isolated from animals in IBE (red) than in torpor (blue). Values are means of state 3 respiration. Asterisks indicate significant difference (p < 0.05, t test). Modified with permission from ref. .
Figure 13. Figure 13. A representation of liver mitochondrial state 3 respiration rates (measured in vitro at 37°C with 6 mmol/L succinate, 1 μmol/L rotenone and 0.2 mmol/L ADP) during different stages of a typical torpor bout in I. tridecemlineatus. When mitochondria are isolated from animals in torpor, respiration is low. During arousal respiration increases, but not until IBE, where T b is ∼37 °C, does it reach maximal values. In contrast, respiration is rapidly and maximally suppressed in the early stages of torpor when T b is still fairly high. Modified with permission from ref. .
Figure 14. Figure 14. Schematic of circannual cycle of body mass, food intake, and metabolism in a lab‐maintained rodent hibernator. Taken from ref. , with permission.
Figure 15. Figure 15. Schematic representation of changes in plasma metabolite concentrations between seasons and hibernation states in thirteen lined ground squirrels. Clusters of plasma metabolites shift in abundance with the nested metabolic cycles of hibernation. Sampling point abbreviations; SA, summer active; IBA, interbout aroused (equivalent to IBE); Ent, entrance into a torpor bout; LT, late in a torpor bout; Ar, arousal. Other abbreviations; AAs, amino acids; FFAs, free fatty acids. From ref. , used with permission.
Figure 16. Figure 16. Dry muscle mass (g) of eight skeletal muscles from active and aestivating Cyclorana alboguttata (N = 10). The letters a and b, and x, y, and z indicate significant differences. Values are means ± s.e.m. Taken from ref. with permission.


Figure 1. The effect of ambient (environmental) temperature on the metabolic rate of a typical nontorpid endotherm (e.g., a small eutherian mammal; red line) and an ectotherm vertebrate (blue line) of similar mass. Between 27 and 36°C (the Thermal Neutral Zone [TNZ], bounded by dashed lines) the endotherm metabolic rate is minimal, and T b is maintained near 37°C by regulating heat loss, for example, through alterations in piloerection and peripheral blood flow. Below 27°C, the endotherm must increase thermogenesis, that is, increases in metabolism solely for the sake of producing more heat (e.g., shivering, activation of BAT) to defend T b. The T b of the ectotherm is very close to the ambient temperature and metabolism is regulated largely by passive thermal effects on enzyme‐catalyzed reactions. Note the different scales on the two axes. For more details, consult ref. .


Figure 2. The ETS of a typical animal. The enzyme complexes are associated with the inner mitochondrial membrane (IMM). NADH, derived from the Krebs cycle, is oxidized by complex I and succinate by complex II. Electrons from these substrates are transferred to the mobile carrier coenzyme Q (Q), which transfers them to complex III, and subsequently to complex IV via cytochrome C (C). Approximately 40% of free energy released by substrate oxidation is used by complexes I, III, and IV to pump protons from the matrix to the intermembrane space (IMS), between the IMM and the outer mitochondrial membrane (OMM). The remainder of the free energy is released as heat. In the presence of ADP, derived from ATPase‐catalyzed ATP hydrolysis, protons return to the matrix, powering ATP synthesis by complex V. The IMM of eutherian mammal BAT contain little complex V but, uniquely, significant amounts of UCP1. When BAT adipocytes are activated by sympathetic nervous stimulation, protons flow from the IMS to the matrix through UCP1, stimulating ETS substrate oxidation and heat production, but no ATP synthesis.


Figure 3. Phylogenetic tree showing mammalian orders with species that use hibernation (H) or torpor (T). Modified with permission from ref. .


Figure 4. Avian phylogenetic tree showing families with species where adults display torpor (T) or possible hibernation (H?). Modified with permission from ref. .


Figure 5. Body composition of young‐of‐the‐year thirteen‐lined ground squirrels. Shortly after weaning animals were weighed and body composition was determined using quantitative H+ nuclear magnetic resonance. See ref. for experimental details. Values are means ± standard error of three males and four females from the same litter. J.F. Staples, D.J. Chung, and C.G. Guglielmo, unpublished data.


Figure 6. The effect of food quantity and PUFA content on hibernation in eastern chipmunks (Tamias striatus). Animals were fed either on natural forage (Control) or had their diet supplemented with food that had a similar PUFA content to the natural diet (Natural PUFA) or with food containing higher PUFA than the natural diet (High PUFA). Data from ref. with permission.


Figure 7. Fasting induced daily torpor in mice (Mus musculus). Body temperature T b of two individual Balb/c mice over the course of a week during which fasting occurred. Photophase began at 9 pm, and scotophase (black bars) began at 9 am. Fasting began just prior to the start of the scotophase on Monday (7 am) and ended 3 days later. Prior to fasting, mice maintained a fairly constant T b and torpor was not observed. Once fasting began, T b became more variable, and bouts of daily torpor occurred, where T b dropped below 31°C (indicated by dashed line). These mice underwent one or more bouts of daily torpor on each of the 3 days of fasting. Once food was returned, T b stabilized near 37°C, and no bouts of torpor were observed. Modified from ref. with permission.


Figure 8. Core body temperature of a thirteen lined ground squirrel through several torpor bouts at the beginning of the hibernation season (A). Metabolic rate and body temperature of a ground squirrel in the different stages of a torpor bout (B). Modified from ref. with permission.


Figure 9. Body temperature and metabolic rate of a Djungarian hamster showing a spontaneous bout of daily torpor. Modified from ref. with permission.


Figure 10. (A) Activity of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) in different phases of hibernation bout in Syrian hamsters. “Summer” and “Winter” animals were euthermic (T b ∼ 37°C). “IBA” = interbout arousal (equivalent to IBE), “cooling” = entrance. Groups differing significantly (p < 0.01, Tukey's post‐hoc comparisons) are denoted by different superscripts. (B) The effect of cardiac sarcoplasmic reticulum phospholipid fatty acid composition on Ca2+ ATPase activity in different phases of a hibernation bout. Ca2+ ATPase activity as a function of the proportions (% of total fatty acids) linoleic acid (LA 18:2, n‐6) (a), docosahexaenoic acid (DHA 22:6, n‐3) (b), and (c) the ratio of LA/DHA. Black dots indicate data from torpid animals, black triangles from cooling animals, grey dots from animals during interbout arousals, and open dots from nonhibernating summer and winter Syrian hamsters. Modified from ref. .


Figure 11. (A) The content of cytochrome a in liver mitochondria isolated from Ictidomys tridecemlineatus does not differ significantly between torpor and IBE. (B) State 3 respiration (with 10 mmol/L succinate as substrate plus 1 μmol/L rotenone and 0.2 mmol/L ADP) of liver mitochondria isolated from torpid ground squirrels is suppressed by approximately 65% whether expressed relative to mitochondrial protein or cytochrome a content. Asterisk indicates significant difference (p < 0.05, t test). K. Mathers, R. Balaban, J. Staples, unpublished data.


Figure 12. The effect of in vitro assay temperature on the respiration of liver mitochondria isolated from a hibernator, Ictidomys tridecemlineatus. At 37 and 25°C, state 3 respiration (in the presence of 10 mmol/L succinate, 1 μmol/L rotenone, and 0.2 mmol/L ADP) is significantly higher when isolated from animals in IBE (red) than in torpor (blue). Values are means of state 3 respiration. Asterisks indicate significant difference (p < 0.05, t test). Modified with permission from ref. .


Figure 13. A representation of liver mitochondrial state 3 respiration rates (measured in vitro at 37°C with 6 mmol/L succinate, 1 μmol/L rotenone and 0.2 mmol/L ADP) during different stages of a typical torpor bout in I. tridecemlineatus. When mitochondria are isolated from animals in torpor, respiration is low. During arousal respiration increases, but not until IBE, where T b is ∼37 °C, does it reach maximal values. In contrast, respiration is rapidly and maximally suppressed in the early stages of torpor when T b is still fairly high. Modified with permission from ref. .


Figure 14. Schematic of circannual cycle of body mass, food intake, and metabolism in a lab‐maintained rodent hibernator. Taken from ref. , with permission.


Figure 15. Schematic representation of changes in plasma metabolite concentrations between seasons and hibernation states in thirteen lined ground squirrels. Clusters of plasma metabolites shift in abundance with the nested metabolic cycles of hibernation. Sampling point abbreviations; SA, summer active; IBA, interbout aroused (equivalent to IBE); Ent, entrance into a torpor bout; LT, late in a torpor bout; Ar, arousal. Other abbreviations; AAs, amino acids; FFAs, free fatty acids. From ref. , used with permission.


Figure 16. Dry muscle mass (g) of eight skeletal muscles from active and aestivating Cyclorana alboguttata (N = 10). The letters a and b, and x, y, and z indicate significant differences. Values are means ± s.e.m. Taken from ref. with permission.
References
 1. Adamczewski JZ , Gates CC , Hudson RJ , Price MA . Seasonal changes in body composition of mature female caribou and calves (Rangifer tarandus groenlandicus) on an arctic island with limited winter resources. Can J Zool 65: 1149‐1157, 1987.
 2. Ahlquist D , Nelson R , Steiger D , Jones J , Ellefson R . Glycerol metabolism in the hibernating black bear. J Comp Physiol B 155: 75‐79, 1984.
 3. Anderson KA , Hirschey MD . Mitochondrial protein acetylation regulates metabolism. Essays Biochem 52: 23‐35, 2012.
 4. Andres‐Mateos E , Mejias R , Soleimani A , Lin BM , Burks TN , Marx R , Lin B , Zellars RC , Zhang Y , Huso DL , Marr TG , Leinwand LA , Merriman DK , Cohn RD . Impaired skeletal muscle regeneration in the absence of fibrosis during hibernation in 13‐lined ground squirrels. PLoS One 7: e48884, 2012.
 5. Andrews MT . Advances in molecular biology of hibernation in mammals. Bioessays 29: 431‐440, 2007.
 6. Andrews MT , Russeth KP , Drewes LR , Henry P‐G . Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol 296: R383‐R393, 2009.
 7. Arendt T , Bullmann T . Neuronal plasticity in hibernation and the proposed role of the microtubule‐associated protein tau as a “master switch” regulating synaptic gain in neuronal networks. Am J Physiol 305: R478‐R489, 2013.
 8. Armitage KB , Shulenberger E . Evidence for a circannual metabolic cycle in Citellus tridecemlineatus, a hibernator. Comp Biochem Physiol 42A: 667‐688, 1972.
 9. Armstrong C , Staples J . The role of succinate dehydrogenase and oxaloacetate in metabolic suppression during hibernation and arousal. J Comp Physiol B 180: 775‐783, 2010.
 10. Armstrong C , Thomas RH , Price ER , Guglielmo CG , Staples JF . Remodeling mitochondrial membranes during arousal from hibernation. Physiol Biochem Zool 84: 438‐449, 2011.
 11. Armstrong C , Thomas RH , Price ER , Guglielmo CG , Staples JF . Remodeling mitochondrial membranes during arousal from hibernation. Physiol Biochem Zool 84: 438‐449, 2011.
 12. Arnold W . Social thermoregulation during hibernation in alpine marmots (Marmota marmota). J Comp Physiol B 158: 151‐156, 1988.
 13. Arnold W , Ruf T , Frey‐Roos F , Bruns U . Diet‐independent remodeling of cellular membranes precedes seasonally changing body temperature in a hibernator. PLoS One 6: e18641, 2011.
 14. Bakko EB , Porter WP , Wunder BA . Body temperature patterns in black‐tailed prairie dogs in the field. Can J Zool 66: 1783‐1789, 1988.
 15. Balaban RS . Regulation of oxidative phosphorylation in the mammalian cell. Am J Physiol 258: C377‐C389, 1990.
 16. Barger J , Brand MD , Barnes BM , Boyer BB . Tissue‐specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels. Am J Physiol 284: R1306‐R1313, 2003.
 17. Barnes B . Relationships between hibernation and reproduction in male ground squirrels. In: Geiser F , Hulbert AJ , Nichol SC , editors. Adaptations to the Cold. Armidale, NSW: University of New England Press, 1996, pp. 71‐80.
 18. Barnes BM . Freeze avoidance in a mammal: Body temperatures below 0°C in an arctic hibernator. Science 244: 1593‐1595, 1989.
 19. Bennis C , Cheval L , Buffin‐Meyer B , Younes‐Ibrahim M , Barlet‐Bas C , Marsy S , Doucet A . Cold‐ and ouabain‐resistance of renal Na,K‐ATPase in cold‐exposed and hibernating Jerboas (Jaculus orientalis). Comp Biochem Physiol A 117: 493‐500, 1997.
 20. Bickler PE . CO2 balance of a heterothermic rodent: Comparison of sleep, torpor, and awake states. Am J Physiol 246: R49‐R55, 1984.
 21. Bieber C , Lebl K , Stalder G , Geiser F , Ruf T . Body mass dependent use of hibernation: Why not prolong the active season, if they can? Funct Ecol 28: 167‐177, 2014.
 22. Bishop T , Ocloo A , Brand MD . Structure and function of mitochondria in hepatopancreas cells from metabolically depressed snails. Physiol Biochem Zool 75: 134‐144, 2002.
 23. Bishop T , St‐Pierre J , Brand MD . Primary causes of decreased mitochondrial oxygen consumption during metabolic depression in snail cells. Am J Physiol 282: R372‐R382, 2002.
 24. Blackstone E , Morrison M , Roth MB . H2S induces a suspended animation‐like state in mice. Science 308: 518, 2005.
 25. Bogren LK , Olson JM , Carpluk J , Moore JM , Drew KL . Resistance to systemic inflammation and multi‐organ damage after global ischemia/reperfusion in the Arctic ground squirrel. PLoS One 9: e94225, 2014.
 26. Bolling SF , Tramontini NL , Kilgore KS , Su T‐P , Oeltgen PhD PR , Harlow HH . Use of “natural” hibernation induction triggers for myocardial protection. Ann Thoracic Surg 64: 623‐627, 1997.
 27. Boulant JA . Role of the preoptic‐anterior hypothalamus in thermoregulation and fever. Clin Infect Dis 31: S157‐S161, 2000.
 28. Bouma HR , Kroese FGM , Kok JW , Talaei F , Boerema AS , Herwig A , Draghiciu O , van Buiten A , Epema AH , van Dam A , Strijkstra AM , Henning RH . Low body temperature governs the decline of circulating lymphocytes during hibernation through sphingosine‐1‐phosphate. Proc Natl Acad Sci 108: 2052‐2057, 2011.
 29. Boutilier RG , Donohoe PH , Tattersall GJ , West TG . Hypometabolic homeostasis in overwintering aquatic amphibians. J Exp Biol 200: 387‐400, 1997.
 30. Boyles JG , Dunbar MB , Storm JJ , Brack V . Energy availability influences microclimate selection of hibernating bats. J Exp Biol 210: 4345‐4350, 2007.
 31. Braulke LJ , Heldmaier G . Torpor and ultradian rhythms require an intact signalling of the sympathetic nervous system. Cryobiol 60: 198‐203, 2010.
 32. Brigham RM , Geiser F . Do red squirrels (Tamiasciurus hudsonicus) use daily torpor during winter? Ecoscience 19: 127‐132, 2012.
 33. Brigham RM , McKechnie AE , Doucette LI , Geiser F . Heterothermy in Caprimulgid birds: A review of inter‐ and intraspecific variation in free‐ranging populations. In: Ruf T , Bieber C , Arnold W , Millesi E , editors. Living in a Seasonal World. Heidelberg: Springer, 2012, pp. 175‐187.
 34. Brigham RM , Willis CKR , Geiser F , Mzilikazi N . Baby in the bathwater: Should we abandon the use of body temperature thresholds to quantify expression of torpor? J Therm Biol 36: 376‐379, 2011.
 35. Brooks NE , Myburgh KH , KB . Myostatin levels in skeletal muscle of hibernating ground squirrels. J Exp Biol 214: 2522‐2527, 2011.
 36. Brooks SPJ , Storey KB . Mechanisms of glycolytic control during hibernation in the ground squirrel Spermophilus lateralis . J Comp Physiol B 162: 23‐28, 1992.
 37. Brown GC , Lakin‐Thomas PL , Brand MD . Control of respiration and oxidative phosphorylation in isolated liver cells. Eur J Biochem 192: 355‐362, 1990.
 38. Brown JCL , Chung DJ , Belgrave KR , Staples JF . Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen‐lined ground squirrels. Am J Physiol 302: R15‐R28, 2012.
 39. Brown JCL , Chung DJ , Cooper AN , Staples JF . Regulation of succinate‐fuelled mitochondrial respiration in liver and skeletal muscle of hibernating thirteen‐lined ground squirrels. J Exp Biol 216: 1736‐1743, 2013.
 40. Brown JCL , Gerson AR , Staples JF . Mitochondrial metabolism during daily torpor in the dwarf Siberian hamster: The role of active regulated changes and passive thermal effects. Am J Physiol 293: R1835‐R1845, 2007.
 41. Brown JCL , Marshall KE , Staples JF . Differences in tissue concentrations of hydrogen peroxide in the roots and cotyledons of annual and perennial species of flax (Linum). Botany 90: 1015‐1027, 2012.
 42. Brown JCL , Staples JF . Mitochondrial metabolism during fasting‐induced daily torpor in mice. Biochim Biophys Acta 1797: 476‐486, 2010.
 43. Brown JCL , Staples JF . Mitochondrial metabolic suppression in fasting and daily torpor: Consequences for reactive oxygen species production. Physiol Biochem Zool 84: 467‐480, 2011.
 44. Bruce DS , Darling NK , Seesland KJ , Oeltgen PR , Nilekhani SP , Amstrup SC . Is the polar bear (Ursus maritimus) a hibernator?: Continued studies on opioids and hibernation. Pharmacol Biochem Behav 35: 705‐711, 1990.
 45. Buck C , Barnes B . Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator. Am J Physiol 279: R255‐R262, 2000.
 46. Buck L , Hogg DWR , Rodgers‐Garlick C , Pamenter ME . Oxygen sensitive synaptic neurotransmission in anoxia‐tolerant turtle Cerebrocortex. In: Nurse CA , Gonzalez C , Peers C , Prabhakar N , editors. Arterial Chemoreception SE‐10 (758 ed.). The Netherlands: Springer, 2012, pp. 71‐79.
 47. Buck LC , Barnes BM . Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator. Am J Physiol 279: R255‐R262, 2000.
 48. Buck LT , Hochachka PW . Anoxic suppression of Na+‐K+‐ATPase and constant membrane potential in hepatocytes: Support for channel arrest. Am J Physiol 265: R1020‐R1025, 1993.
 49. Buck LT , Hochachka PW , Schon A , Gnaiger E . Microcalorimetric measurement of reversible metabolic suppression induced by anoxia in isolated hepatocytes. Am J Physiol 265: R1014‐R1019, 1993.
 50. Buck LT , Land SC , Hochachka PW . Anoxia‐tolerant hepatocytes: model system for study of reversible metabolic suppression. Am J Physiol 265: R49‐R56, 1993.
 51. Buck LT , Pamenter ME . Adaptive responses of vertebrate neurons to anoxia ‐ matching supply to demand. Resp Physiol Neurobiol 154: 226‐240, 2006.
 52. Buck MJ , Squire TL and Andrews MT . Coordinate expression of the PDK4 gene: A means of regulating fuel selection in a hibernating mammal. Physiol Genom 8: 5‐13, 2002.
 53. Burlington RF , Darvish AD . Low‐temperature performance of isolated working hearts from a hibernator and a nonhibernator. Physiol Zool 61: 387‐395, 1988.
 54. Burlington RF , Klain GJ . Gluconeogenesis during hibernation and arousal from hibernation. Comp Biochem Physiol 22: 701‐708, 1967.
 55. Canale C , Levesque D , Lovegrove B . Tropical heterothermy: Does the exception prove the rule or force a re‐definition? In: Ruf T , Bieber C , Arnold W , Millesi ED , editors. Living in a Seasonal World SE‐3. Berlin Heidelberg: Springer, 2012, pp. 29‐40.
 56. Castellini MA , Rea LD . The biochemistry of natural fasting at its limits. Experientia 48: 575‐582, 1992.
 57. Chance B , Leigh JS , Clark BJ , Maris J , Kent J , Nioka S , Smith D . Control of oxidative metabolism and oxygen delivery in human skeletal muscle: A steady‐state analysis of the work/energy cost transfer function. Proc Natl Acad Sci U S A 82: 8384‐8388, 1985.
 58. Chance B , Williams GR . Respiratory enzymes in oxidative phosphorylation. J Biol Chem 217: 395‐408, 1955.
 59. Charnock JS , Simonson LP . Seasonal variations in the renal cortical (Na+ + K+)‐ATPase and Mg2+‐ATPase of a hibernator, the ground squirrel (Spermophilus richardsonii). Comp Biochem Physiol 60B: 433‐439, 1978.
 60. Chen Y , Matsushita M , Nairn AC , Damuni Z , Cai D , Frerichs KU , Hallenbeck JM . Mechanisms for increased levels of phosphorylation of elongation factor‐2 during hibernation in ground squirrel. Biochem 40: 11565‐11570, 2001.
 61. Christian K , Green B , Kennett R . Some physiological consequences of estivation by freshwater crocodiles, Crocodylus johnstoni . J Herpetol 30: 1‐9, 1996.
 62. Christian KA , Bedford GS , Schultz TJ . Energetic consequences of metabolic depression in tropical and temperate‐zone lizards. Aust J Zool 47: 133‐141, 1999.
 63. Christian SL , Ross AP , Zhao HW , Kristenson HJ , Zhan X , Rasley BT , Bickler PE , Drew KL . Arctic ground squirrel (Spermophilus parryii) hippocampal neurons tolerate prolonged oxygen‐glucose deprivation and maintain baseline ERK1/2 and JNK activation despite drastic ATP loss. J Cereb Blood Flow Metab 28: 1307‐1319, 2008.
 64. Chung D , Lloyd GP , Thomas RH , Guglielmo CG , Staples JF . Mitochondrial respiration and succinate dehydrogenase are suppressed early during entrance into a hibernation bout, but membrane remodeling is only transient. J Comp Physiol B 181: 699‐711, 2011.
 65. Chung DJ , Szyszka B , Brown JCL , Hüner NPA , Staples JF . Changes in the mitochondrial phosphoproteome during mammalian hibernation. Physiol Genomics 45: 389‐399, 2013.
 66. Cimen H , Han M‐J , Yang Y , Tong Q , Koc H , Koc EC . Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochem 49: 304‐311, 2010.
 67. Cooper AN , Brown JCL , Staples JF . Are long chain acyl CoAs responsible for suppression of mitochondrial metabolism in hibernating 13‐lined ground squirrels? Comp Biochem Physiol B 170: 50‐57, 2014.
 68. Costa IASF , Driedzic WR , Gamperl AK . Metabolic and cardiac responses of cunner tautogolabrus adspersus to seasonal and acute changes in temperature. Physiol Biochem Zool 86: 233‐244, 2013.
 69. Cotton CJ , Harlow HJ . Avoidance of skeletal muscle atrophy in spontaneous and facultative hibernators. Physiol Biochem Zool 83: 551‐560, 2010.
 70. Cuddihee RW , Fonda ML . Concentrations of lactate and pyruvate and temperature effects on lactate dehydrogenase activity in the tissues of the big brown bat (Eptesicus fuscus) during arousal from hibernation. Comp Biochem Physiol B 73: 1001‐1009, 1982.
 71. Daan S , Barnes BM , Strijkstra AM . Warming up for sleep‐ground squirrels sleep during arousals from hibernation. Neurosci Letts 128: 265‐268, 1991.
 72. Dausmann KH , Glos J , Ganzhorn JU , Heldmaier G . Physiology: Hibernation in a tropical primate. Nature 429: 825‐826, 2004.
 73. Daussman KH , Nowack J , Kobbe S , Mzilikazi N . Afrotropical heterothermy: A continuum of possibilities. In: Ruf T , Bieber C , Arnold W , Millesi E , editors. Living in a Seasonal World. Berlin: Springer, 2012, pp. 13‐28.
 74. Dave KR , Prado R , Raval AP , Drew KL , Perez‐Pinzon MA . The Arctic ground squirrel brain is resistant to injury from cardiac arrest during euthermia. Stroke 37: 1261‐1265, 2006.
 75. Davis TRA , Johnston DR , Bell FC , Cremer BJ . Regulation of shivering and non‐shivering heat production during acclimation in rats. Am J Physiol 198: 471‐475, 1960.
 76. Davis WL , Goodman DBP , Crawford LA , Cooper OJ , Matthews JL . Hibernation activates glyoxylate cycle and gluconeogenesis in black bear brown adiose tissue. Biochim Biophys Acta 1051: 276‐278, 1990.
 77. Dawe AR , Spurrier WA . Hibernation induced in ground squirrels by blood transfusion. Science 163: 298‐299, 1969.
 78. Diaz MB , Lange M , Heldmaier G , Klingenspor M . Depression of transcription and translation during daily torpor in the Djungarian hamster (Phodopus sungorus). J Comp Physiol B 174: 495‐502, 2004.
 79. Divakaruni AS , Brand MD . The regulation and physiology of mitochondrial proton leak. Physiology 26: 192‐205, 2011.
 80. Doherty AH , Florant GL , Donahue SW . Endocrine regulation of bone and energy metabolism in hibernating mammals. Integr Comp Biol 54: 463‐483, 2014.
 81. Donohoe P , West T , Boutilier R . Factors affecting membrane permeability and ionic homeostasis in the cold‐submerged frog. J Exp Biol 203: 405‐414, 2000.
 82. Donohoe PH , Boutilier RG . The protective effect of metabolic rate depression in hypoxic cold submerged frogs. Resp Phys 111: 325‐336, 1998.
 83. Drew KL , Harris MB , LaManna JC , Smith MA , Zhu XW , Ma YL . Hypoxia tolerance in mammalian heterotherms. J Exp Biol 207: 3155‐3162, 2004.
 84. Dukoff DJ , Hogg DW , Hawrysh PJ , Buck LT . Scavenging ROS dramatically increase NMDA receptor whole‐cell currents in painted turtle cortical neurons. J Exp Biol 217: 3346‐3355, 2014.
 85. Eddy SF , Morin P , Storey KB . Differential expression of selected mitochondrial genes in hibernating little brown bats, Myotis lucifugus. J Exp Zool A 305: 620‐630, 2006.
 86. Eddy SF , Storey KB . Up‐regulation of fatty acid‐binding proteins during hibernation in the little brown bat, Myotis lucifugus. Biochim Biophys Acta 1676: 63‐70, 2004.
 87. El Hachimi Z , Tijane M , Boissonnet G , Benjouad A , Desmadril M , Yon JM . Regulation of the skeletal muscle metabolism during hibernation of Jaculus orientalis . Comp Biochem Physiol 96B: 457‐459, 1990.
 88. Else PL , Wu BJ . What role for membranes in determining the higher sodium pump molecular activity of mammals compared to ectotherms? J Comp Physiol B 169: 296‐302, 1999.
 89. Elvert R , Heldmaier G . Retention of carbon dioxide during entrance into torpor in dormice. In: Heldmaier G , Klingenspor M , editors. Life in the Cold. Berlin: Springer, 2000, pp. 179‐186.
 90. Elvert R , and Heldmaier G . Cardiorespiratory and metabolic reactions during entrance into torpor in dormice, Glis glis . J Exp Biol 208: 1373‐1383, 2005.
 91. English TE , Storey KB . Enzymes of adenylate metabolism and their role in hibernation of the white‐tailed prairie dog, Cynomys leucurus. Arch Biochem Biophys 376: 91‐100, 2000.
 92. Epperson LE , Karimpour‐Fard A , Hunter LE , Martin SL . Metabolic cycles in a circannual hibernator. Physiol Genomics 43: 799‐807, 2011.
 93. Epperson LE , Rose JC , Carey HV , Martin SL . Seasonal proteomic changes reveal molecular adaptations to preserve and replenish liver proteins during ground squirrel hibernation. Am J Physiol 298: R329‐R340, 2010.
 94. Fedotcheva NI , Litvinova EG , Kamzolova SV , Morgunov IG , Amerkhanov ZG . Mitochondrial metabolites in tissues as indicators of metabolic alterations during hibernation. Cryoletters 31: 392‐400, 2010.
 95. Fenn AM , Zervanos SM , Florant GL . Energetic relationships between field and laboratory woodchucks (Marmota monax) along a latitudinal gradient. Ethol Ecol Evol 21: 299‐315, 2009.
 96. Fishman AP , Pack AI , Delaney RC , Galante RJ . Estivation in Protopterus . J Morphol Supp 1: 237‐248, 1986.
 97. Florant G , Healy J . The regulation of food intake in mammalian hibernators: A review. J Comp Physiol B 182: 451‐467, 2012.
 98. Florant G , Porst H , Peiffer A , Hudachek S , Pittman C , Summers SA , Rajala M , Scherer P . Fat‐cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow‐bellied marmots (Marmota flaviventris). J Comp PhysiolB 174: 633‐639, 2004.
 99. Florant GL . Lipid metabolism in hibernators: The importance of essential fatty acids. Amer Zool 38: 331‐340, 1988.
 100. Frank C , Brooks SJ , Harlow H , Storey K . The influence of hibernation patterns on the critical enzymes of lipogenesis and lipolysis in prairie dogs. Exp Biol Online 3: 1‐8, 1998.
 101. Frank CL . The influence of dietary fatty acids on hibernation by golden‐mantled ground squirrels (Spermophlilus lateralis). Physiol Zool 65: 906‐920, 1992.
 102. Frank CL . Polyunsaturate content and diet selection by ground squirrels (Spermophilus lateralis). Ecology 75: 458‐463, 1994.
 103. Frank CL , Karpovich S , Barnes BM . Dietary fatty acid composition and the hibernation patterns in free‐ranging Arctic ground squirrels. Physiol Biochem Zool 81: 486‐495, 2008.
 104. French AR . Allometries of the durations of torpid and euthermic intervals during mammalian hibernation: A test of the theory of metabolic control of the timing of changes in body temperature. J Comp Physiol 156: 13‐19, 1985.
 105. Frerichs KU , Smith CB , Brenner M , DeGracia DJ , Krause GS , Marrone L , Dever TE , Hallenbeck JM . Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation. Proc Natl Acad Sci U S A 95: 14511‐14516, 1998.
 106. Frick NT , Bystriansky JS , Ip YK , Chew SF , Ballantyne JS . Lipid, ketone body and oxidative metabolism in the African lungfish, Protopterus dolloi following 60 days of fasting and aestivation. Comp Biochem Physiol A 151: 93‐101, 2008.
 107. Frick NT , Bystriansky JS , Ip YK , Chew SF , Ballantyne JS . Cytochrome c oxidase is regulated by modulations in protein expression and mitochondrial membrane phospholipid composition in estivating African lungfish. Am J Physiol 298: R608‐R616, 2010.
 108. Gallagher K , Staples JF . Metabolism of brain cortex and cardiac muscle mitochondria in hibernating 13‐lined ground squirrels Ictidomys tridecemlineatus. Physiol Biochem Zool 86: 1‐8, 2013.
 109. Galster WA , Morrison PR . Cyclic changes in carbohydrate concentration during hibernation in the arctic ground squirrel. Am J Physiol 218: 1228‐1232, 1970.
 110. Galster WA , Morrison PR . Gluconeogenesis in arctic ground squirrels between periods of hibernation. Am J Physiol 228: 325‐330, 1975.
 111. Gao Y‐F , Wang J , Wang H‐P , Feng B , Dang K , Wang Q , Hinghofer‐Szalkay HG . Skeletal muscle is protected from disuse in hibernating dauria ground squirrels. Comp Biochem Physiol A 161: 296‐300, 2012.
 112. Gavrilova O , Leon LR , Marcus‐Samuels B , Mason MM , Castle AL , Refetoff S , Vinson C , Reitman ML . Torpor in mice is induced by both leptin‐dependent and ‐independent mechanisms. Proc Natl Acad Sci U S A 96: 14623‐14628, 1999.
 113. Gehnrich SC , Aprille JR . Hepatic gluconeogenesis and mitochondrial function during hibernation. Comp Biochem Physiol 91B: 11‐16, 1988.
 114. Geiser F . 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, 1991.
 115. Geiser F . Evolution of daily torpor and hibernation in birds and mammals: Importance of body size. Clin Exp Pharmacol Physiol 25: 736‐740, 1998.
 116. Geiser F . Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66: 239‐273, 2004.
 117. Geiser F . Aestivation in mammals and birds. In: Arturo Navas C , Carvalho J , editors. Aestivation SE‐5 (49 ed.). Berlin Heidelberg: Springer, 2010, pp. 95‐111.
 118. Geiser F , Heldmaier G . The impact of dietary fats, photoperiod, temperature and season on morphological variables, torpor patterns, and brown adipose tissue fatty acid composition of hamsters, Phodopus sungorus. J Comp Physiol B 165: 406‐415, 1995.
 119. Geiser F , Kenagy GJ . Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator. Am J Physiol 252: R897‐R901, 1987.
 120. Gerson AR , Brown JCL , Thomas R , Bernards MA , Staples JF . Effects of dietary polyunsaturated fatty acids on mitochondrial metabolism in mammalian hibernation. J Exp Biol 211: 2689‐2699, 2008.
 121. Giroud S , Frare C , Strijkstra A , Boerema A , Arnold W , Ruf T . Membrane phospholipid fatty acid composition regulates cardiac SERCA activity in a hibernator, the Syrian Hamster (Mesocricetus auratus). PLoS One 8: e63111, 2013.
 122. Grabek KR , Karimpour‐Fard A , Epperson LE , Hindle A , Hunter LE , Martin SL . Multistate proteomics analysis reveals novel strategies used by a hibernator to precondition the heart and conserve ATP for winter heterothermy. Physiol Genomics 43: 1263‐1275, 2011.
 123. Grimpo K , Legler K , Heldmaier G , Exner C . That's hot: Golden spiny mice display torpor even at high ambient temperatures. J Comp Physiol B 183: 567‐581, 2013.
 124. Groom DJE , Kuchel L , Richards JG . Metabolic responses of the South American ornate horned frog (Ceratophrys ornata) to estivation. Comp Biochem Physiol B 164: 2‐9, 2013.
 125. Guglielmo CG , McGuire LP , Gerson AR , Seewagen CL . Simple, rapid, and non‐invasive measurement of fat, lean, and total water masses of live birds using quantitative magnetic resonance. J Ornithol 152: 75‐85, 2011.
 126. Hampton M , Melvin RG , Andrews MT . Transcriptomic analysis of brown adipose tissue across the physiological extremes of natural hibernation. PLoS One 8: e85157, 2013.
 127. Hand LE , Saer BRC , Hui ST , Jinnah HA , Steinlechner S , Loudon ASI , Bechtold DA . Induction of the metabolic regulator Txnip in fasting‐induced and natural torpor. Endocrinol 154: 2081‐2091, 2013.
 128. Hand SC , Menze MA , Borcar A , Patil Y , Covi JA , Reynolds JA , Toner M . Metabolic restructuring during energy‐limited states: Insights from Artemia franciscana embryos and other animals. J Insect Physiol 57: 584‐594, 2011.
 129. Hand SC , Somero GN . Phosphofructokinase of the hibernator Citellus beecheyi: Temperature and pH regulation of activity via influences on the tetramer‐dimer equilibrium. Physiol Zool 56: 380‐388, 1983.
 130. Haouzi P , Notet V , Chenuel B , Chalon B , Sponne I , Ogier V , Bihain B . H2S induced hypometabolism in mice is missing in sedated sheep. Respir Physiol Neurobiol 160: 109‐115, 2008.
 131. Harlow HJ , Frank CL . The role of dietary fatty acids in the evolution of spontaneous and facultative hibernation patterns in prairie dogs. J Comp Physiol B 171: 77‐84, 2001.
 132. Hayasaka S , Kimihiko O , Tanabe K , Saisho T , Shinomiya A . On the habitat of Nautilus pompilius in Tanon Strait (Phillipines) and Fiji Islands. In: Saunders WB , Landman NH , editors. Nautilus. New York: Plenum Press, 1987, pp. 179‐200.
 133. Heldmaier G , Elvert R . How to enter torpor: Thermodynamic and physiological mechanisms of metabolic depression. In: Barnes BM , Carey HV , editors. Life in the Cold. Fairbanks: University of Alaska Fairbanks, 2004, pp. 185‐198.
 134. Heldmaier G , Klingenspor M , Werneyer M , Lampi GJ , Brooks SPJ , Storey KB . Metabolic adjustments during daily torpor in the Djungarian hamster. Am J Physiol 276: E896‐E906, 1999.
 135. Heldmaier G , Ortmann S , Elvert R . Natural hypometabolism during hibernation and daily torpor in mammals. Resp Physiol Neurobiol 141: 317‐329, 2004.
 136. Heller HC , Colliver GW , Beard J . Thermoregulation during entrance into hibernation. Pflugers Arch 369: 55‐59, 1977.
 137. Henry P‐G , Russeth KP , Tkac I , Drewes LR , Andrews MT , Gruetter R . Brain energy metabolism and neurotransmission at near‐freezing temperatures: in vivo 1H MRS study of a hibernating mammal. J Neurochem 101: 1505‐1515, 2007.
 138. Hiebert SM , Fulkerson EK , Lindermayer, KT , McClure, SD . Effect of temperature on preference for dietary unsaturated fatty acids in the Djungarian hamster (Phodopus sungorus). Can J Zool 78: 1361‐1368, 2000.
 139. Hindle AG , Grabek KR , Epperson LE , Karimpour‐Fard A , Martin SL . Metabolic changes associated with the long winter fast dominate the liver proteome in 13‐lined ground squirrels. Physiol Genomics 46: 348‐361, 2014.
 140. Hindle AG , Karimpour‐Fard A , Epperson LE , Hunter LE , Martin SL . Skeletal muscle proteomics: Carbohydrate metabolism oscillates with seasonal and torpor‐arousal physiology of hibernation. Am J Physiol 301: R1440‐R1452, 2011.
 141. Hindle AG , Martin SL . Intrinsic circannual regulation of brown adipose tissue form and function in tune with hibernation. Am J Physiol 306: E284‐E299, 2014.
 142. Hirschey MD , Shimazu T , Goetzman E , Jing E , Schwer B , Lombard DB , Grueter CA , Harris C , Biddinger S , Ilkayeva OR , Stevens RD , Li Y , Saha AK , Ruderman NB , Bain JR , Newgard CB , Farese Jr RV , Alt FW , Kahn CR , Verdin E . SIRT3 regulates mitochondrial fatty‐acid oxidation by reversible enzyme deacetylation. Nature 464: 121‐125, 2010.
 143. Hittel D , Storey KB . Differential expression of adipose‐ and heart‐type fatty acid binding proteins in hibernating ground squirrels. Biochim Biophys Acta 1522: 238‐243, 2001.
 144. Hochachka PW , Guppy M . Metabolic Arrest and the Control of Biological Time. Cambridge Mass.: Harvard University Press, 1987.
 145. Hochachka PW , Somero GN . Biochemical Adaptation. Princeton, N.J.: Princeton University Press, 1984.
 146. Hong J , Sigg DC , Coles JA , Oeltgen PR , Harlow HJ , Soule CL , Iaizzo PA . Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle. Muscle Nerve 32: 200‐207, 2005.
 147. Humphries MM , Kramer DL , Thomas DW . The role of energy availability in mammalian hibernation: an experimental test in free‐ranging eastern chipmunks. Physiol Biochem Zool 76: 180‐186, 2003.
 148. Hwang YT , Lariviere S , Messier F . Energetic consequences and ecological significance of heterothermy and social thermoregulation in striped skunks (Mephitis mephitis). Physiol Biochem Zool 80: 138‐145, 2007.
 149. IUPS. Glossary of terms for thermal physiology. J Therm Biol 28: 75‐106, 2003.
 150. Jackson DC , Ultsch GR . Physiology of hibernation under the ice by turtles and frogs. J Exp Zool A 313A: 311‐327, 2010.
 151. James RS , Staples JF , Brown JCL , Tessier SN , Storey KB . The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen‐lined ground squirrel, Ictidomys tridecemlineatus . J Exp Biol 216: 2587‐2594, 2013.
 152. Jefimow Mg , Ostrowski M , Jakubowska, Anna , Wojciechowski MS . The effects of dietary cholesterol on metabolism and daily torpor patterns in Siberian hamsters. Physiol Biochem Zool 87: 527‐538, 2014.
 153. Jinka TR , Tøien Ø , Drew KL . Season primes the brain in an Arctic hibernator to facilitate entrance into torpor mediated by adenosine A1 receptors. J Neurosci 31: 10752‐10758, 2011.
 154. Johansson BW . The hibernator heart ‐ nature's model of resistance to ventricular fibrillation. Cardiovasc Res 31: 826‐832, 1996.
 155. Jonasson KA , Willis CKR . Hibernation energetics of free‐ranging little brown bats. J Exp Biol 215: 2141‐2149, 2012.
 156. Jones JD , Burnett P , Zollman P . The glyoxylate cycle: Does it function in the dormant or active bear? Comp Biochem Physiol B 124: 177‐179, 1999.
 157. Karpovich S , Tøien Ø , Buck C , Barnes B . Energetics of arousal episodes in hibernating arctic ground squirrels. J Comp Physiol B 179: 691‐700, 2009.
 158. Kayes SM , Cramp RL , Hudson NJ , Franklin CE . Surviving the drought: Burrowing frogs save energy by increasing mitochondrial coupling. J Exp Biol 212: 2248‐2253, 2009.
 159. Kayes SM , Cramp RL , Hudson NJ , Franklin CE . Effect of opioids on tissue metabolism in aestivating and active green‐striped burrowing frogs, Cyclorana alboguttata . J Herpetol 47: 369‐377, 2013.
 160. Christian K , Webb JK , Schultz T ., Green B . Effects of seasonal variation in prey abundance on field metabolism, water flux, and activity of a tropical ambush foraging snake. Physiol Biochem Zool 80: 522‐533, 2007.
 161. Kiss T , Battonyai I , Pirger Z . Down regulation of sodium channels in the central nervous system of hibernating snails. Physiol Behav 131: 93‐98, 2014.
 162. Klingenspor M , Fromme T . Brown adipose tissue. In: Adipose Tissue Biology. New York: Springer, 2012, pp. 39‐69.
 163. Kondo N , Kondo J . Identification of novel blood proteins specific for mammalian hibernation. J Biol Chem 267: 473‐478, 1992.
 164. Kondo N , Sekijima T , Kondo J , Takamatsu N , Tohya K , Ohtsu T . Circannual control of hibernation by HP complex in the brain. Cell 125: 161‐172, 2006.
 165. Kronfeld‐Schor N , Richardson C , Silvia BA , Kunz TH , Widmaier EP . Dissociation of leptin secretion and adiposity during prehibernatory fattening in little brown bats. Am J Physiol 279: R1277‐R1281, 2000.
 166. Kurtz C , Lindell S , Mangino M , Carey H . Hibernation confers resistance to intestinal ischemia‐reperfusion injury. Am J Physiol 291: G895‐G901, 2006.
 167. Kutschke M , Grimpo K , Kastl A , Schneider S , Heldmaier G , Exner C , Jastroch M . Depression of mitochondrial respiration during daily torpor of the Djungarian hamster, Phodopus sungorus, is specific for liver and correlates with body temperature. Comp Biochem Physiol A 164: 584‐589, 2013.
 168. Land SC , Buck LT , Hochachka PW . Response of protein synthesis to anoxia and recovery in anoxia‐tolerant hepatocytes. Am J Physiol 264: R41‐R48, 1993.
 169. Land SC , Hochachka PW . Protein turnover during metabolic arrest in turtle hepatocytes: role and energy dependence of proteolysis. Am J Physiol 266: C1028‐C1036, 1994.
 170. Larivée ML , Boutin S , Speakman JR , McAdam AG , Humphries MM . Associations between over‐winter survival and resting metabolic rate in juvenile North American red squirrels. Funct Ecol 24: 597‐607, 2010.
 171. Larson J , Drew KL , Folkow LP , Milton SL , Park TJ . No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates. J Exp Biol 217: 1024‐1039, 2014.
 172. LeBlanc PJ , Obbard M , Battersby BJ , Felskie AK , Brown L , Wright PA , Ballantyne JS . Correlations of plasma lipid metabolites with hibernation and lactation in wild black bears Ursus americanus . J Comp Physiol B 171: 327‐334, 2001.
 173. Lee I , Salomon AR , Ficarro S , Mathes I , Lottspeich F , Grossman LI , Hüttemann M . cAMP‐dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity. J Biol Chem 280: 6094‐6100, 2005.
 174. Lee K , Park JY , Yoo W , Gwag T , Lee J‐W , Byun M‐W , Choi I . Overcoming muscle atrophy in a hibernating mammal despite prolonged disuse in dormancy: Proteomic and molecular assessment. J Cell Biochem 104: 642‐656, 2008.
 175. Lehmer EM , Savage ST , Antolin MF , Biggins BE . Extreme plasticity in thermoregulatory behaviors of free ranging black‐tailed prairie dogs. Physiol Biochem Zool 79: 454‐467, 2006.
 176. Lewis JM , Driedzic WR . Tissue‐specific changes in protein synthesis associated with seasonal metabolic depression and recovery in the north temperate labrid, Tautogolabrus adspersus . Am J Physiol Regul Integr Comp Physiol 293: R474‐R481, 2007.
 177. Lin DC , Hershey JD , Mattoon JS , Robbins CT . Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation. J Exp Biol 215: 2081‐2087, 2012.
 178. Lindell SL , Klahn SL , Piazza TM , Mangino MJ , Torrealba JR , Southard JH , Carey HV . Natural resistance to liver cold ischemia‐reperfusion injury associated with the hibernation phenotype. Am J Physiol 288: G473‐G480, 2005.
 179. Lovegrove B. A single origin of heterothermy in mammals. In: Ruf T , Bieber C , Arnold W , Millesi E, editors. Living in a Seasonal World SE‐1. Berlin Heidelberg: Springer, 2012, pp. 3‐11.
 180. Lovegrove BG . The evolution of endothermy in Cenozoic mammals: A plesiomorphic‐apomorphic continuum. Biol Rev 87: 128‐162, 2012.
 181. Luis AD , Hudson PJ . Hibernation patterns in mammals: A role for bacterial growth? Funct Ecol 20: 471‐477, 2006.
 182. Ma YL , Zhu X , Rivera PM , Tøien Ø , Barnes BM , LaManna JC , Smith MA , Drew KL . Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Am J Physiol 289: R1297‐R1306, 2005.
 183. MacDonald JA , Storey KB . Regulation of ground squirrel Na+K+‐ATPase activity by reversible phosphorylation during hibernation. Biochem Biophys Res Comm 254: 424‐429, 1999.
 184. MacMillan HA , Williams CM , Staples JF , Sinclair BJ . Reestablishment of ion homeostasis during chill‐coma recovery in the cricket Gryllus pennsylvanicus . Proc Natl Acad Sci U S A 109: 20750‐20755, 2012.
 185. Malysheva AN , Storey KB , Lopina OD , Rubstov AM . Ca‐ATPase activity and protein composition of sarcoplasmic reticulum membranes isolated from skeletal muscles of typical hibernator, the ground squirrel Spermophilus undulatus. Biosci Rep 21: 831‐838, 2001.
 186. Mantle BL , Hudson NJ , Harper GS , Cramp RL , Franklin CE . Skeletal muscle atrophy occurs slowly and selectively during prolonged aestivation in Cyclorana alboguttata (Günther 1867). J Exp Biol 212: 3664‐3672, 2009.
 187. Martin AW , Fuhrman FA . The relationship between summated tissue respiration and metabolic rate in the mouse and dog. Physiol Zool 28: 18‐28, 1955.
 188. Martin SL , Epperson LE . A two‐switch model for mammalian hibernation. In: Lovegrove BG , McKechnie AE , editors. Hypometabolism in Animals. Pietermaritzburg: Interpak Books, 2008, pp. 177‐186.
 189. McGee‐Lawrence ME , Stoll DM , Mantila ER , Fahrner BK , Carey HV , Donahue SW . Thirteen‐lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength. J Exp Biol 214: 1240‐1247, 2011.
 190. McGee‐Lawrence ME , Wojda SJ , Barlow LN , Drummer TD , Castillo AB , Kennedy O , Condon KW , Auger J , Black HL , Nelson OL , Robbins CT , Donahue SW . Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation). Bone 45: 1186‐1191, 2009.
 191. McGee ME , Maki AJ , Johnson SE , Nelson OL , Robbins CT , Donahue SW . Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis). Bone 42: 396‐404, 2008.
 192. McKechnie AE , Lovegrove BG . Avian facultative hypothermic responses: A review. Condor 104: 705‐724, 2002.
 193. McKee G , Andrews JF . Brown adipose tissue is the main source of energy during arousal of the golden hamster (Mesocricetus auratus). Comp Biochem Physiol 96A: 485‐488, 1990.
 194. Melvin RG , Andrews MT . Torpor induction in mammals: Recent discoveries fueling new ideas. Trends Endocrinol Metab 20: 490‐498, 2009.
 195. Milner R , Wang L , Trayhurn P . Brown fat thermogenesis during hibernation and arousal in Richardson's ground squirrel. Am J Physiol 256: R42‐R48, 1989.
 196. Milsom WK , Andrade DV , Brito SP , Toledo LF , Wang T , Abe AS . Seasonal changes in daily metabolic patterns of Tegu lizards (Tupinambis merianae) placed in the cold (17°C) and dark. Physiol Biochem Zool 81: 165‐175, 2008.
 197. Milsom WK , Jackson DC . Hibernation and gas exchange. Compr Physiol 1: 397‐420, 2011.
 198. Mitrovic D , Dymowska A , Nilsson GE , Perry SF . Physiological consequences of gill remodeling in goldfish (Carassius auratus) during exposure to long‐term hypoxia. Am J Physiol 297: R224‐R234, 2009.
 199. Moberly WRD . Hibernation in the desert Iguana, Dipsosaurus dorsalis . Physiol Zool 36: 152‐160, 1963.
 200. Muleme HM , Walpole AC , Staples JF . Mitochondrial metabolism in hibernation: Metabolic suppression, temperature effects, and substrate preferences. Physiol Biochem Zool 79: 474‐483, 2006.
 201. Munro D , Thomad DW , Humphries MM . Torpor patterns of hibernating eastern chipmunks Tamias striatus vary in response to the size and fatty acid composition of food hoards. J Anim Ecol 74: 692‐700, 2005.
 202. Murie JO , Boag DA . The relationship of body weight to overwinter survival in Columbian ground squirrels. J Mammal 65: 688‐690, 1984.
 203. Musacchia XJ , Steffen JM , Steffen MC , Geoghegan TE , Dombrowski JM , Milsom WK , Burlington RF . Morphometric and biochemical adaptations of skeletal muscle in hibernating and non‐hibernating grounds squirrels. In: Malan A , Canguilhem B , editors. Living in the Cold. London: John Libbey/Eurotext, 1989, pp. 217‐224.
 204. Nedergaard J , Cannon B . Preferential utilization of brown adipose tissue lipids during arousal from hibernation in hamsters. Am J Physiol 247: R506‐R512, 1984.
 205. Nelson BT , Ding X , Boney‐Montoya J , Gerard RD , Kliewer SA , Andrews MT . Metabolic hormone FGF21 is induced in ground squirrels during hibernation but its overexpression is not sufficient to cause torpor. PLoS One 8: e53574, 2013.
 206. Nelson CJ , Otis JP , Martin SL , Carey HV . Analysis of the hibernation cycle using LC‐MS‐based metabolomics in ground squirrel liver. Physiol Genomics 37: 43‐51, 2009.
 207. Nelson OL , Jansen Heiko T , Galbreath E , Morgenstern K , Gehring Jamie L , Rigano Kimberly S , Lee J , Gong J , Shaywitz Adam J , Vella Chantal A , Robbins Charles T , Corbit Kevin C . Grizzly bears exhibit Augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation. Cell Metab 20: 376‐382, 2014.
 208. Nestler J , Lingenfelter T , Gonthier G , Gifford J , Peterson S . Gluconeogenesis in brain and liver during daily torpor in deer mice (Peromyscus maniculatus). In: Heldmaier G , Klingenspor M , editors. Life in the Cold. Berlin: Springer, 2000, pp. 347‐353.
 209. Nestler JR . Relationships between respiratory quotient and metabolic rate during entry to and arousal from daily torpor in deer mice (Peromyscus maniculatus). Physiol Zool 63: 504‐515, 1990.
 210. Nestler JR , Peterson SJ , Smith BD , Heathcock RB , Johanson CR , Sarhou JC , King JC . Glycolytic enzyme binding during entrance to daily torpor in deer mice (Peromyscus maniculatus). Physiol Zool 70: 61‐67, 1997.
 211. Nicholls DG , Ferguson SJ . Bioenergetics 3. Amsterdam: Academic Press, 2002.
 212. Nizielski SE , Billington CJ , Levine AS . Brown fat GDP binding and circulating metabolites during hibernation and arousal. Am J Physiol 257: R536‐R541, 1989.
 213. Nowell MM , Choi H , Rourke BC . Muscle plasticity in hibernating ground squirrels (Spermophilus lateralis) is induced by seasonal, but not low‐temperature, mechanisms. J Comp Physiol B 181: 147‐164, 2011.
 214. Nurnberger F , Lee TF , Jourdan ML , Wang LCH . Seasonal changes in methionine‐enkephalin immunoreactivity in the brain of a hibernator, Spermophilus columbianus . Br Res 547: 115‐121, 1991.
 215. Oeltgen PR , Bergmann LC , Spurrier WA , Jones SB . Isolation of a hibernation inducing trigger(s) from the plasma of hibernating woodchucks. Prep Biochem 8: 171‐188, 1978.
 216. Oeltgen PR , Nilekani SP , Nuchols PA , Spurrier WA , Su TP , Chien S , Proffitt GE , Mahony C . Identification of the opioid receptor ligand(s) involved in summer‐induced and natural winter hibernation. In: Malan A , Canguilhem B , editors. Living in the Cold II. London: John Libbey, 1989, pp. 97‐101.
 217. Oeltgen PR , Spurrier WA . Characterization of a hibernation induction trigger. In: Musacchia XJ , Jansky L , editors. Survival in the Cold. Amsterdam: Elsevier, 1981, pp. 139‐157.
 218. Oeltgen PR , Walsh JW , Hamann SR , Randall DC , Spurrier WA , Myers RD . Hibernation “trigger”: Opioid‐like inhibitory action on brain function of the monkey. Pharmacol Biochem Behav 17: 1271‐1274, 1982.
 219. Orr AL , Lohse LA , Drew KL , Hermes‐Lima M . Physiological oxidative stress after arousal from hibernation in Arctic ground squirrel. Comp Biochem Physiol A 153: 213‐221, 2009.
 220. Osborne PG , Hashimoto M . Brain antioxidant levels in hamsters during hibernation, arousal and cenothermia. Behav Brain Res 168: 208‐214, 2006.
 221. Otis J , Ackermann L , Denning G , Carey H . Identification of qRT‐PCR reference genes for analysis of opioid gene expression in a hibernator. J Comp Physiol B 180: 619‐629, 2010.
 222. Pan P , van Breukelen F . Preference of IRES‐mediated initiation of translation during hibernation in golden‐mantled ground squirrels, Spermophilus lateralis. Am J Physiol 301: R370‐R377, 2011.
 223. Pedler S , Fuery CJ , Withers PC , Flanigan J , Guppy M . Effectors of metabolic depression in an estivating pulmonate snail (Helix aspersa): Whole animal and in vitro tissue studies. J Comp Physiol B 166: 375‐381, 1996.
 224. Pehowich DJ . Modification of skeletal muscle sarcoplasmic reticulum fatty acyl composition during arousal from hibernation. Comp Biochem Physiol 109B: 571‐578, 1994.
 225. Pengelley ET , Asmundson SJ , Barnes B , Aloia RC . Relationship of light intensity and photoperiod to circannual rhythmicity in the hibernating ground squirrel, Citellus lateralis. Comp Biochem Physiol A 53: 273‐277, 1976.
 226. Pengelley ET , Fisher KC . The effect of temperature and photoperiod on the yearly hibernating behaviour of captive golden‐mantled ground squirrels (Citellus lateralis tescorum). Can J Zool 41: 1103‐1120, 1963.
 227. Phillips D , Covian R , Aponte AM , Glancy B , Taylor JF , Chess D , Balaban RS . Regulation of oxidative phosphorylation complex activity: Effects of tissue‐specific metabolic stress within an allometric series and acute changes in workload. Am J Physiol 302: R1034‐R1048, 2012.
 228. Pinder AW , Storey KB , Urltsch GR . Estivation and Hibernation. In: Feder ME , Burggren WM , editors. Environmental Physiology of the Amphibians. Chicago: University of Chicago Press, 1992, pp. 250‐275.
 229. Plaxton WC . Principles of metabolic control. In: Storey KB , editor. Functional Metabolism. Hobocken, NJ: John Wiley & Son, 2004, pp. 1‐24.
 230. Podrabsky JE , Lopez JP , Fan TWM , Higashi R , Somero GN . Extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus: insights from a metabolomics analysis. J Exp Biol 210: 2253‐2266, 2007.
 231. Popovic V . Cardiac output in hibernating ground squirrels. Am J Physiol 207: 1345‐1348, 1964.
 232. Prendergast BJ , Freeman DA , Zucker I , Nelson RJ . Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels. Am J Physiol 282: R1054‐R1062, 2002.
 233. Price ER , Armstrong C , Guglielmo, Christopher G , Staples JF . Selective mobilization of saturated fatty acids in isolated adipocytes of hibernating 13‐lined ground squirrels Ictidomys tridecemlineatus. Physiol Biochem Zool 86: 205‐212,.
 234. Ramnanan C , Allan M , Groom A , Storey K . Regulation of global protein translation and protein degradation in aerobic dormancy. Mol Cell Biochem 323: 9‐20, 2009.
 235. Ramnanan CJ , McMullen DC , Bielecki A , Storey KB . Regulation of sarcoendoplasmic reticulum Ca2+‐ATPase (SERCA) in turtle muscle and liver during acute exposure to anoxia. J Exp Biol 213: 17‐25, 2010.
 236. Ramnanan CJ , Storey KB . Suppression of Na+/K+‐ATPase activity during estivation in the land snail Otala lactea . J Exp Biol 209: 677‐688, 2006.
 237. Rees BB , Hand SC . Heat dissipation, gas exchange and acid‐base status in the land snail Oreohelix during short‐term estivation. J Exp Biol 152: 77‐92, 1990.
 238. Reilly BD , Hickey AJR , Cramp RL , Franklin CE . Decreased hydrogen peroxide production and mitochondrial respiration in skeletal muscle but not cardiac muscle of the green‐striped burrowing frog, a natural model of muscle disuse. J Exp Biol 217: 1087‐1093, 2014.
 239. Revsbech IG , Shen X , Chakravarti R , Jensen FB , Thiel B , Evans AL , Kindberg J , Fröbert O , Stuehr DJ , Kevil CG , Fago A . Hydrogen sulfide and nitric oxide metabolites in the blood of free‐ranging brown bears and their potential roles in hibernation. Free Radical Biol Med 73: 349‐357, 2014.
 240. Riek A , Geiser F . Allometry of thermal variables in mammals: consequences of body size and phylogeny. Biol Rev 88: 564‐572, 2013.
 241. Rolfe DFS , Brown GC . Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77: 731‐758, 1997.
 242. Rolfe DFS , Newman JMB , Buckingham JA , Clark MG , Brand MD . Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR. Am J Physiol 276: C692‐C699, 1999.
 243. Ross AP , Christian SL , Zhao HW , Drew KL . Persistent tolerance to oxygen and nutrient deprivation and N‐methyl‐D‐aspartate in cultured hippocampal slices from hibernating Arctic ground squirrel. J Cereb Blood Flow Metab 26: 1148‐1156, 2006.
 244. Rosser SP , Bruce DS . Induction of summer hibernation in the 13‐lined ground squirrel, Citellus tridecemlineatus. Cryobiol 15: 113‐116, 1978.
 245. Ruf T , Geiser F . Daily torpor and hibernation in birds and mammals. Biol Rev 90: 891‐926, 2014.
 246. Ruf T , Klingenspor M , Preis H , Heldmaier G . Daily torpor in the Djungarian hamster (Phodopus sungorus): Interactions with food intake, activity, and social behaviour. J Comp Physiol B 160: 609‐615, 1991.
 247. Russell R , O'Neill P , Epperson L , Martin S . Extensive use of torpor in 13‐lined ground squirrels in the fall prior to cold exposure. J Comp Physiol B 180: 1165‐1172, 2010.
 248. Sadho B , Evans AL , Arnemo JM , Fröbert O , Särndahl E , Blanc S . Body temperature during hibernation is highly correlated with a decrease in circulating innate immune cells in the brown bear (Ursus arctos): A common feature among hibernators? Int J Med Sci 10: 508‐514, 2013.
 249. Schoch G , Trinczek B , Bode C . Localization of catalytic and regulatory subunits of cyclic AMP‐dependent protein kinases in mitochondria from various rat tissues. Biochem J 270: 181‐188, 1990.
 250. Secor SM . Digestive physiology of the Burmese python: Broad regulation of integrated performance. J Exp Biol 211:3767‐3774, 2008.
 251. Sekijima T , Ishinawa H , Kondo N . Phylogenetic background of hibernation and hibernation‐specific proteins in sciuridae. In: Ruf T , Bieber C , Arnold W , Millesi E , editors. Living in a Seasonal World. Berlin: Springer, 2012, pp. 327‐335.
 252. Seldin MM , Byerly MS , Petersen PS , Swanson R , Balkema‐Buschmann A , Groschup MH , Wong GW . Seasonal oscillation of liver‐derived hibernation protein complex in the central nervous system of non‐hibernating mammals. J Exp Biol 217: 2667‐2679, 2014.
 253. Serkova NJ , Rose JC , Epperson LE , Carey HV , Martin SL . Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13‐lined ground squirrels by NMR. Physiol Genomics 31: 15‐24, 2007.
 254. Sheriff M , Williams C , Kenagy GJ , Buck CL , Barnes B . Thermoregulatory changes anticipate hibernation onset by 45 days: Data from free‐living arctic ground squirrels. J Comp Physiol B 182: 841‐847, 2012.
 255. Sheriff MJ , Fridinger RW , Tøien Ø , Barnes BM , Buck CL . Metabolic rate and prehibernation fattening in free‐living arctic ground Squirrels. Physiol Biochem Zool 86: 515‐527, 2013.
 256. Sinclair BJ , Stinziano JR , Williams CM , MacMillan HA , Marshall KE , Storey KB . Real‐time measurement of metabolic rate during freezing and thawing of the wood frog, Rana sylvatica: implications for overwinter energy use. J Exp Biol 216: 292‐302, 2013.
 257. Singer D , Bach F , Bretschneider HJ , Kuhn H‐J . Metabolic size allometry and the limits to beneficial metabolic reduction: hypothesis of a uniform specific minimal metabolic rate. In: Hochachka PW , Lutz PL , Sick T , Rosenthal M , Thillart Gvd , editors. Surviving Hypoxia. Boca Raton, FL: CRC Press Inc., 1993, pp. 447‐458.
 258. Snapp BD , Heller HC . Suppression of metabolism during hibernation in ground squirrels (Citellus lateralis). Physiol Zool 54: 297‐307, 1981.
 259. Speakman JR , Król E . The heat dissipation limit theory and evolution of life histories in endotherms time to dispose of the disposable soma theory? Integr Comp Biol 50: 93‐807, 2010.
 260. Squire TL , Lowe ME , Bauer VW , Andrews MT . Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold‐adapted function and differential expression. Physiol Genom 16: 131‐140, 2003.
 261. Srere HK , Wang LCH , Martin SL . Central role for differential gene expression in mammalian hibernation. Proc Natl Acad Sci U S A 89: 7119‐7123, 1992.
 262. St‐Pierre J , Brand MD , Boutilier RG . The effect of metabolic depression on proton leak rate in mitochondria from hibernating frogs. J Exp Biol 203: 1469‐1476, 2000.
 263. St‐Pierre J , Tattersall GJ , Boutilier RG . Metabolic depression and enhanced O2 affinity of mitochondria in hypoxic hypometabolism. Am J Physiol 279: R1205‐R1214, 2000.
 264. Stamper JL , Dark J , Zucker I . Photoperiod modulates torpor and food intake in Siberian hamsters challenged with metabolic inhibitors. Physiol Behav 66: 113‐118, 1999.
 265. Staples JF . Maintaining metabolic balance in mammalian hibernation and daily torpor. In: Nowakowska A , Caputa M , editors. Hypometabolism: Strategies of Survival in Vertebrates and Invertebrates. Kerala India: Research Signpost, 2011, pp. 95‐115.
 266. Staples JF . Metabolic suppression in mammalian hibernation: the role of mitochondria. J Exp Biol 217: 2032‐2036, 2014.
 267. Staples JF , Brown JCL . Mitochondrial metabolism in hibernation and daily torpor: a review. J Comp Physiol B 178: 811‐827, 2008.
 268. Staples JF , Buck LT . Matching cellular metabolic supply and demand in energy‐stressed animals. Comp Biochem Physiol A 153: 95‐105, 2009.
 269. Staples JF , Hochachka PW . Liver energy metabolism during hibernation in the golden‐mantled ground squirrel, Spermophilus lateralis . Can J Zool 74: 1059‐1065, 1997.
 270. Staples JF , Hochachka PW . The effect of hibernation status and cold‐acclimation on hepatocyte gluconeogenesis in the golden‐mantled ground squirrel (Spermophilus lateralis). Can J Zool 76: 1734‐1740, 1998.
 271. Staples JF , Kajimura M , Wood CM , Patel M , Ip YK , McClelland GB . Enzymatic and mitochondrial responses to 5 months of aerial exposure in the slender lungfish Protopterus dolloi Boulenger. J Fish Biol 73: 608‐622, 2008.
 272. Storey KB . Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation. J Biol Chem 262: 1670‐1673, 1987.
 273. Storey KB . Survivial under stress: molecular mechanisms of metabolic rate depression in animals. S Afr J Zool 33: 55‐64, 1998.
 274. Storey KB , Kelly DA . Glycolysis and energetics in organs of hibernating mice (Zapus hudsonius). Can J Zool 73: 202‐207, 1995.
 275. Storey KB , Storey JM . Aestivation: signaling and hypometabolism. J Exp Biol 215: 1425‐1433, 2012.
 276. Strijkstra AM , Koopmans T , Bouma HR , de Boer SF , Hut RA , Boerema AS . On the dissimilarity of 5′‐AMP induced hypothermia and torpor in mice. In: Ruf T , Bieber C , Arnold W , Millesi E, editors. Living in a Seasonal World. Berlin Heidelberg: Springer, 2012, pp. 351‐362.
 277. Suozzi A , Malatesta M , Zancanaro C . Subcellular distribution of key enzymes of lipid metabolism during the euthermia‐hibernation‐arousal cycle. J Anat 214: 956‐962, 2009.
 278. Swoap SJ , Rathvon M , Gutilla M . AMP does not induce torpor. Am J Physiol 293: R468‐R473, 2007.
 279. Swoap SJ , Weinshenker D . Norepinephrine controls both torpor initiation and emergence via distinct mechanisms in the mouse. PLoS One 3: e4038, 2008.
 280. Takamatsu N , Ohba K , Kondo J , Kondo N , Shiba T . Hibernation associated gene regulation of plasma proteins with a collagen‐like domain in mammalian hibernators. Mol Cell Biol 13: 1516‐1521, 1993.
 281. Talaei F , Hylkema MN , Bouma HR , Boerema AS , Strijkstra AM , Henning RH , Schmidt M . Reversible remodeling of lung tissue during hibernation in the Syrian hamster. J Exp Biol 214: 1276‐1282, 2011.
 282. Tattersall GJ , Sinclair BJ , Withers PC , Fields PA , Seebacher F , Cooper CE , Maloney SK . Coping with thermal challenges: Physiological adaptations to environmental temperatures. Compr Physiol 2: 2151‐2202, 2012.
 283. Tessier S , Storey K . Expression of myocyte enhancer factor‐2 and downstream genes in ground squirrel skeletal muscle during hibernation. Mol Cell Biochem 344: 151‐162, 2010.
 284. Tøien Ø , Blake J , Edgar DM , Grahn DA , Heller HC , Barnes BM . Hibernation in black bears: Independence of metabolic suppression from body temperature. Science 331: 906‐909, 2011.
 285. Tøien Ø , Drew KL , Chao ML , Rice ME . Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels. Am J Physiol 281: R572‐R583, 2001.
 286. Tomitsuka E , Kita K , Esumi H . Regulation of succinate‐ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit. Proc Japan Acad B 85: 258‐265, 2009.
 287. Utz JC , Nelson S , O'Toole BJ and van Breukelen F . Bone strength is maintained after 8 months of inactivity in hibernating golden‐mantled ground squirrels, Spermophilus lateralis . J Exp Biol 212: 2746‐2752, 2009.
 288. Valsecchi F , Ramos‐Espiritu LS , Buck J , Levin LR , Manfredi G . cAMP and Mitochondria. Physiology 28: 199‐209, 2013.
 289. van Breukelen F , Martin SL . Translational initiation is uncoupled from elongation at 18°C during mammalian hibernation. Am J Physiol 281: R1374‐R1379, 2001.
 290. van Breukelen F , Martin SL . Molecular adaptations in mammalian hibernators: Unique adaptations or generalized responses. J Appl Physiol 92: 2640‐2647, 2002.
 291. van Breukelen F , Martin SL . Reversible depression of transcription during hibernation. J Comp Physiol B 172: 355‐361, 2002.
 292. van Breukelen F , Sonenberg N , Martin SL . Seasonal and state‐dependent changes of eIF4E and 4E‐BP1 during mammalian hibernation: Implications for the control of translation during torpor. Am J Physiol: R349‐R353, 2004.
 293. Velickovska V , Lloyd BP , Qureshi S , van Breukelen F . Proteolysis is depressed during torpor in hibernators at the level of the 20S core protease. J Comp Physiol B 175: 329‐335, 2005.
 294. Velickovska V , van Breukelen F . Ubiquitylation of proteins in livers of hibernating golden‐mantled ground squirrels, Spermophilus lateralis. Cryobiol 55: 230‐235, 2007.
 295. Wang LCH , Belke D , Jourdan ML , Lee TF , Nurnberger F . The “hibernation induction trigger”: Specificity and validity of bioassay using the 13‐lined ground squirrel. Cryobiol 25: 355‐362, 1988.
 296. Wang LCH , Lee TF . Torpor and hibernation in mammals: Metabolic, physiological, and biochemical adaptations. Compr Physiol Supp. 14: Handbook of Physiology, Environmental Physiology: 507‐532, 2011.
 297. Wang LCH , McArthur MD , Jourdan ML , Lee T . Depressed metabolic rates in hibernation and hypothermia: Can these be compared meaningfully? In: Sutton JR , Coates G , Remmers JE , editors. Hypoxia. Toronto: B.C. Decker, 1990, pp. 78‐83.
 298. Wang LCH , Wolowyk MW . Torpor in mammals and birds. Can J Zool 66: 133‐137, 1988.
 299. Wang P , Walter RD , Bhat BG , Florant GL , Coleman RA . Seasonal changes in enzymes of lipogenesis and triacylglycerol synthesis in the golden‐mantled ground squirrel (Spermophilus lateralis). Comp Biochem Physiology B 118: 261‐267, 1997.
 300. Wang SQ , Lakatta EG , Cheng H , Zhou ZQ . Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators. J Exp Biol 205: 2957‐2962, 2002.
 301. Wang Y , Ezemaduka AN , Tang Y , Chang Z . Understanding the mechanism of the dormant dauer formation of C. elegans: From genetics to biochemistry. IUBMB Life 61: 607‐612, 2009.
 302. Ward JM , Armitage KB . Circannual rhythms of food consumption, body mass and metabolism in yellow‐bellied marmots. Comp Biochem Physiol 69A: 621‐626, 1981.
 303. Weitten M , Robin J‐P , Oudart H , Pévet P , Habold C . Hormonal changes and energy substrate availability during the hibernation cycle of Syrian hamsters. Horm Behav 64: 611‐617, 2013.
 304. West TG , Boutilier RG . Metabolic suppression in anoxic frog muscle. J Comp Physiol 168: 273‐280, 1998.
 305. Williams CT , Barnes BM , Kenagy GJ , Buck CL . Phenology of hibernation and reproduction in ground squirrels: Integration of environmental cues with endogenous programming. J Zool 292: 112‐124, 2014.
 306. Wilson BE , Deeb S , Florant GL . Seasonal changes in hormone‐sensitve lipase mRNA concentrations in marmot white adipose tissue. Am J Physiol 262: R177‐R181, 1992.
 307. Wilz M , Heldmaier G . Comparison of hibernation, estivation and daily torpor in the edible dormouse, Glis glis. J Comp Physiol B 170: 511‐521, 2000.
 308. Wojda SJ , McGee‐Lawrence ME , Gridley RA , Auger J , Black HL , Donahue SW . Yellow‐bellied Marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation. Bone 50: 182‐188, 2012.
 309. Xu Y , Shao C , Fedorov V , Goropashnaya A , Barnes B , Yan J . Molecular signatures of mammalian hibernation: comparisons with alternative phenotypes. BMC Genomics 14: 567, 2013.
 310. Yatani A , Kim S‐J , Kudej RK , Wang Q , Depre C , Irie K , Kranias EG , Vatner SF , Vatner DE . Insights into cardioprotection obtained from study of cellular Ca2+ handling in myocardium of true hibernating mammals. Am J Physiol 286: H2219‐H2228, 2004.
 311. Young KM , Cramp RL , Franklin CE . Each to their own: Skeletal muscles of different function use different biochemical strategies during aestivation at high temperature. J Exp Biol 216: 1012‐1024, 2013.
 312. Young KM , Cramp RL , Franklin CE . Hot and steady: Elevated temperatures do not enhance muscle disuse atrophy during prolonged aestivation in the ectotherm Cyclorana alboguttata . J Morphol 274: 165‐174, 2013.
 313. Zervanos SM , Maher CR , Florant GL . Effect of body mass on hibernation strategies of woodchucks (Marmota monax). Integr Comp Biol 54: 443‐451, 2014.
 314. Zervanos Stam M , Maher Christine R , Waldvogel Jerry A , Florant Gregory L . Latitudinal differences in the hibernation characteristics of woodchucks (Marmota monax). Physiol Biochem Zool 83: 135‐141, 2010.
 315. Zhao HW , Ross AP , Christian SL , Buchholz JN , Drew KL . Decreased NR1 phosphorylation and decreased NMDAR function in hibernating Arctic ground squirrels. J Neurosci Res 84: 291‐298, 2006.

Related Articles:

Coping with Thermal Challenges: Physiological Adaptations to Environmental Temperatures
Behavioral Thermoregulation in the Cold
Hibernation and Gas Exchange
Torpor and Hibernation in Mammals: Metabolic, Physiological, and Biochemical Adaptations

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

James F. Staples. Metabolic Flexibility: Hibernation, Torpor, and Estivation. Compr Physiol 2016, 6: 737-771. doi: 10.1002/cphy.c140064