Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Hashimoto, Masaaki; Gao, Bihu; Kikuchi-Utsumi, Kazue; Ohinata, Hiroshi; Osborne, Peter G.

doi:10.1016/s0306-4565(02)00024-4

Cited by 13 publications

(17 citation statements)

References 103 publications

(131 reference statements)

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“…BAT from hibernating hamsters was large in size and had abundant UCP1 compared with that from warm-acclimated animals, as has been previously reported (9). BAT thermogenesis produced by the ␤ 3 -adrenergic receptor agonist in hibernating animals was larger at 12°C than in nonhibernating animals; however, this was not observed at 36°C.…”

Section: Discussionsupporting

confidence: 73%

Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

Kitao

Hashimoto

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Kitao N, Hashimoto M. Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters. Am J Physiol Regul Integr Comp Physiol 302: R118 -R125, 2012. First published October 12, 2011 doi:10.1152/ajpregu.00053.2011.-Brown adipose tissue (BAT) is thought to play a significant physiological role during arousal when body temperature rises from the extremely low body temperature that occurs during hibernation. The dominant pathway of BAT thermogenesis occurs through the ␤3-adrenergic receptor. In this study, we investigated the role of the ␤3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vitro and in vivo. Syrian hamsters in the hibernation group contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group. Although the ability of the ␤3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between the hibernation and warm-acclimated groups, its maximum ratio over the basal value at 12°C in the hibernation group was significantly larger than that in the warmacclimated group. Forskolin stimulation at 12°C produced equivalent BAT responses in these two groups. In vivo thermogenesis was assessed with the arousal time determined by the time course of BAT temperature or heart rate. Stimulation of BAT by CL316,243 significantly shortened the time of arousal from hibernation compared with that induced by vehicle alone, and it also induced arousal in deep hibernating animals. The ␤3-antagonist SR59230A inhibited arousal from hibernation either in part or completely. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective ␤3-receptor mechanism at lower temperatures. adaptation; ␤ 3-adrenoceptor mechanism HIBERNATION IS CHARACTERIZED by the depression of energy expenditure and body temperature. Arousing from a hypothermic state requires extensive thermogenesis in the period of a few hours (28), and the mechanism of thermogenesis during this process has been the subject of intense investigation. Increased muscle action potential during arousal from hibernation and lowered arousal rate by curarization suggest that shivering partly but significantly contributes to thermogenesis (12,17,22). It is now widely recognized that brown adipose tissue (BAT) plays a physiologically dominant role in nonshivering thermogenesis (NST) when body temperature rises from an extremely low level during arousal from hibernation (7, 10 -13, 31, 32). Thermogenesis in BAT is physiologically stimulated by norepinephrine released from sympathetic nerve terminals. Transduction of the thermogenic signal occurs mainly through ␤ 3 -adrenergic receptors on the membrane of brown adipocytes and is coupled by adenylyl cyclase activation, resulting in increased cytosolic cAMP levels (44, 45). Increased cAMP then induces hydrolysis of stored triacylglycerol by activating cAMP-dependent PKA....

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Section: Discussionsupporting

confidence: 73%

Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

Kitao

Hashimoto

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Section: (Cenothermia Is the Iups Term Replacing Euthermia [4])mentioning

confidence: 99%

“…Radioactive uridine [5, H] (specific activity: 30 Ci/mmol) and L-leucine [1-14 C] (specific activity: 55 mCi/mmol) were purchased from (American Radiolabeled Chemicals Inc. Missouri, USA). Fourteen hamsters were allocated to one of 4 experimental groups.…”

Section: Animals and Housingmentioning

confidence: 99%

“…Molecularly orientated studies have searched for up-or-down regulation of gene expression in a small number of organs from torpid animals in an attempt to demonstrate molecular changes that are consistent with the enormous physiological changes occurring across the hibernation cycle [5]. Early investigations used radioactively labeled precursors to measure in vivo transcription in brains [6,7], translation in liver [8,9], and more recently translation in brain and heart [10], Abstract: This study measured in vivo synthesis of total RNA and protein from cortex, cerebellum and midbrain/brainstem and 6 major organs from Syrian hamsters (Mesocricetus auratus) during (a) 33 h of torpor (body temperature 5-6°C); (b) 90 min of the early arousal; (c) 90 min of the middle arousal; (d) 90 min in cold adapted cenothermic (CEN) hamsters of the same circannual period.…”

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Determination In Vivo of Newly Synthesized Gene Expression in Hamsters During Phases of the Hibernation Cycle

Osborne

Gao

Hashimoto

2004

JJP

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Hibernation is a circannual adaptation and within the hibernation season, the hibernation cycle of a 'classic' hibernator, such as the Syrian hamster, can be divided into six distinct physiological phases. An entrance phase, when metabolism is inhibited and body temperature decreases [1]. A long period of torpor when metabolic rate (MR) is approximately 2.5% of resting metabolic rate (RMR) [2, 3]. This is followed by an arousal period of three phases: an early arousal phase during which the animal warms anterior crucial organs by non-shivering thermogenesis; a middle arousal phase when shivering thermogenesis is recruited to heat the anterior body to cenothermia (CEN) and a late arousal phase when posterior organs attain CEN and the animal rests or sleeps. An inter-bout arousal phase, of hours to days, during which time the hibernator maintains CEN body temperature before the initiation of another hibernation cycle. At present the onset of the hibernation cycle cannot be predicted. (Cenothermia is the IUPS term replacing euthermia [4]).Molecularly orientated studies have searched for up-or-down regulation of gene expression in a small number of organs from torpid animals in an attempt to demonstrate molecular changes that are consistent with the enormous physiological changes occurring across the hibernation cycle [5]. Early investigations used radioactively labeled precursors to measure in vivo transcription in brains [6,7], translation in liver [8,9], and more recently translation in brain and heart 14 C]-leucine. In torpor, RNA synthesis was 5-25% of CEN levels depending upon tissue. In brain and heart mRNA was not preferentially synthesized. Protein was synthesized at low, tissue specific levels during torpor. Initiation of arousal and the warming of anterior organs via non-shivering thermogenesis during the early arousal occurred without measurable synthesis of RNA or proteins. Tissue specific levels of RNA and protein synthesis occurred later after shivering thermogenesis had been recruited and was strongly influenced by thermal gradients in the body. In the middle arousal phase, protein synthesis is most active in the brain despite modest synthesis of RNA and mRNA. The majority of molecular processing required for the induction and maintenance of torpor and the arousal from torpor up until the onset of shivering thermogenesis occurs during the cenothermic period before the hamster initiates the hibernation cycle. [The Japanese Journal of Physiology 54: [295][296][297][298][299][300][301][302][303][304][305] 2004]

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“…The initial warming phase is associated with nonshivering thermogenesis. In the second phase, shivering thermogenesis is recruited after muscles above the diaphragm have attained a temperature of ϳ20°C, at which point shivering becomes an efficient means of heat production (11). In the final phase, the temperatures of the posterior organs and hindlimbs rapidly increase to cenothermia, metabolic rate decreases (1,20), the animal presents an EEG profile that can be interpreted as slow-wave sleep (12,26), and the proteins and mRNA consumed during the preceding arousal phases and hibernation are replenished by reinitiation of gene transcription and translation (21).…”

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Sympathetic α-adrenergic regulation of blood flow and volume in hamsters arousing from hibernation

Osborne

Sato

Shuke

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Mammals arousing from hibernation display pronounced regional heterothermy, where the thoracic and head regions warm faster than the abdominal and hindlimb regions. We used laser-Doppler flowmetry to measure peripheral hind foot blood flow during hibernation and arousal and gamma imaging of technetium-labeled albumin to measure whole blood volume distribution in hamsters arousing from hibernation. It was discovered that the hibernating hamster responds to physical but not to sound or hypercapnic stimulation with rapid, 73% reduction of hind foot blood flow. Hind foot blood flow vasoconstriction was maintained from the onset of arousal until late in arousal when rectal temperature was rapidly increased. ␣-Adrenergic blockade early in arousal increased hind foot blood flow by 700%, suggesting that vasoconstriction was mediated by activation of sympathetic tone. Gamma imaging revealed that, by the early phase of arousal from hibernation, the blood volume of the body below the liver is greatly reduced, whereas blood volumes of the thorax and head are much greater than corresponding volumes in anesthetized hamsters. As arousal progresses and cardiac activity increases and regional heterothermy develops, this regional blood volume distribution is largely maintained; however, blood volume slowly decreases in the thoracic region and slowly increases in the shoulder and head regions. The rapid increase in rectal temperature, characteristic of mid-to latearousal phases, is probably mediated, in part, by reduction of adrenergic tone on abdominal and hindlimb vasculature. Warm blood then moves into the hind body, produces an increase in temperature, blood flow, and blood volume in the hind body and compensatory reductions of blood volume in the neck, head, and thoracic regions.laser-Doppler flowmetry; gamma imaging; torpor; vasoconstriction THE TRANSITION FROM THE low body temperatures of classical hibernation to cenothermia is associated with probably the most remarkable changes in mammalian circulatory physiology, and yet this has been the subject of few in vivo investigations and remains poorly understood. For small mammals in natural hibernation, body temperature, metabolism (20, 24), heart rate (HR), blood pressure (1, 16), and cerebral blood flow (6,20) are greatly reduced relative to cenothermia. However, despite these enormous reductions in physiological parameters, in vivo studies demonstrate that blood pressure and HR during hibernation remain sensitive to pharmacological activation of ␣-and ␤-adrenergic receptors, respectively (16). Evidence for parasympathetic influences on HR and respiration during hibernation is more equivocal and may only be evident in some species that exhibit episodic breathing (10). Respiratory chemosensitivity to hypercapnic gas is retained at low body temperatures during hibernation (14, 18). Collectively, these results are consistent with the functional conservation of some aspects of cenothermic autonomic regulation during hibernation in hamsters, sciurids, and possibly all other small...

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Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

Cited by 13 publications

References 103 publications

Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

Determination In Vivo of Newly Synthesized Gene Expression in Hamsters During Phases of the Hibernation Cycle

Sympathetic α-adrenergic regulation of blood flow and volume in hamsters arousing from hibernation

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