Unmasking of GDP binding sites on hamster brown adipose tissue mitochondria and uncoupling protein

Henningfield, Mary F.; Swick, Robert W.

doi:10.1016/0305-0491(91)90148-7

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…In this study, 2 wk of continuous exposure to cold and short photoperiod increased the amount of BAT and UCP1 in these animals, thus supporting previous reports that either or both of these cues stimulate BAT growth and UCP1 production (5,21,27,30,33,37,41). Although UCP1 activity, as estimated by the amount of GDP bound to mitochondria, was found to be increasing even at 2 wk after exposure to 4°C, where it then reached a plateau in BAT (14); additional increases of BAT and UCP1 were observed in the animals that entered hibernation, suggesting that a greater thermogenic response is expected in BAT under such conditions. Despite increased UCP1 in the hibernating animals, no significant increase in the maximum rate of oxygen consumption under normothermic conditions was observed.…”

Section: In Vitro Experimentssupporting

confidence: 91%

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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: In Vitro Experimentssupporting

confidence: 91%

“…Future studies should clarify how such high thermogenic capacity at low temperatures can only be obtained through hibernation and not from 2 wk of cold acclimation, which is adequate for adaptation of UCP1 activity (14).…”

Section: In Vivo Experimentsmentioning

confidence: 99%

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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“…A measure that may be related to mitochondrial swelling and that seems to correlate well with mitochondrial activity in brown fat mitochondria is the so-called "unmasking" phenomenon (e.g., Refs. 283,317,339,509). This is a still poorly understood process that reveals itself as an increase in the number of measureable mitochondrial GDP-binding sites, i.e., on UCP1.…”

Section: Parameters Of Activationmentioning

confidence: 99%

Brown Adipose Tissue: Function and Physiological Significance

Cannon

Nedergaard

2004

Physiological Reviews

5,559

126

5,981

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The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogenesis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.

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“…There is still debate about the exact mechanism by which UCP1 exerts this profound mitochondrial uncoupling ( 49–51 ), but the basic function and regulation of UCP1 is felt to be the same between rodent models and humans. UCP1 is downregulated by ATP or other purine nucleotides binding ( 52 , 53 ), and UCP1 binding to radiolabeled guanine nucleotide diphosphate (GDP) has been used as a functional marker of UCP1 activation in vitro ( 54 , 55 ). “Unmasking” of these GDP binding sites occurs in BAT mitochondria after adrenergic or cold stimulation, independent of change in UCP1 protein expression ( 54 , 55 ).…”

Section: Cellular Biology Of Brown Adipose Tissuementioning

confidence: 99%

Brown Adipose Tissue—A Translational Perspective

et al. 2022

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Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography (PET) with 18F-fluorodeoxiglucose ( 18FDG), which can be dissociated from BAT thermogenic activity, as for example in insulin resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride (TG) lipolysis. This lipolytic BAT response is intertwined with that of white adipose and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body’s thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in white adipose and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.

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Unmasking of GDP binding sites on hamster brown adipose tissue mitochondria and uncoupling protein

Cited by 7 publications

References 11 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

Brown Adipose Tissue: Function and Physiological Significance

Brown Adipose Tissue—A Translational Perspective

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