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Metabolic Flexibility: Hibernation, Torpor, and Estivation

James F. Staples

10.1002/cphy.c140064

Source: null

Published online: March 2016

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.

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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. 283.
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. 116.
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. 193.
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. 126 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. 202 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. 42 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. 267 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. 135 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. 122.
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. 38.
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. 266.
Figure 14. Figure 14. Schematic of circannual cycle of body mass, food intake, and metabolism in a lab‐maintained rodent hibernator. Taken from ref. 98, 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. 93, 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. 187 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. 283.


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. 116.


Figure 4. Avian phylogenetic tree showing families with species where adults display torpor (T) or possible hibernation (H?). Modified with permission from ref. 193.


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. 126 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. 202 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. 42 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. 267 with permission.


Figure 9. Body temperature and metabolic rate of a Djungarian hamster showing a spontaneous bout of daily torpor. Modified from ref. 135 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. 122.


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. 38.


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. 266.


Figure 14. Schematic of circannual cycle of body mass, food intake, and metabolism in a lab‐maintained rodent hibernator. Taken from ref. 98, 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. 93, 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. 187 with permission.
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Article Title: Metabolic Flexibility: Hibernation, Torpor, and Estivation
 

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