The Experts below are selected from a list of 2493 Experts worldwide ranked by ideXlab platform
Mark I. Talan - One of the best experts on this subject based on the ideXlab platform.
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the effect of exercise training in cold on shivering and Nonshivering Thermogenesis in adult and aged c57bl 6j mice
Experimental Gerontology, 1998Co-Authors: Vladimir I. Shefer, Mark I. TalanAbstract:To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and Nonshivering Thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced Nonshivering Thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced Nonshivering Thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering Thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering Thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.
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The effect of exercise training in cold on shivering and Nonshivering Thermogenesis in adult and aged C57BL/6J mice.
Experimental Gerontology, 1998Co-Authors: Vladimir I. Shefer, Mark I. TalanAbstract:To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and Nonshivering Thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced Nonshivering Thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced Nonshivering Thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering Thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering Thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.
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Nonshivering Thermogenesis in adult and aged c57bl 6j mice housed at 22 c and at 29 c
Experimental Gerontology, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Nadejda A. KoshelevaAbstract:Abstract Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22°C or at thermoneutrality (29°C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5°C below control level. In separate experiments we measured O 2 consumption and CO 2 production and calculated the Nonshivering Thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and Nonshivering Thermogenesis were lower in animals housed at thermoneutrality (29°C) than in mice housed at 22°. Among mice maintained at 22°C, but not at thermoneutrality, aged animals had greater Nonshivering Thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22°C, showed the changes in Nonshivering Thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.
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cold acclimation associated changes in brown adipose tissue do not necessarily indicate an increase of Nonshivering Thermogenesis in c57bl 6j mice
Physiology & Behavior, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Lori A Clow, Nadejda A. KoshelevaAbstract:We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of Nonshivering Thermogenesis. To understand the origin of this failure, this study was intended to measure Nonshivering Thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint at 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cold acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system.
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Nonshivering Thermogenesis in adult and aged C57BL/6J mice housed at 22°C and at 29°C
Experimental Gerontology, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Nadejda A. KoshelevaAbstract:Abstract Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22°C or at thermoneutrality (29°C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5°C below control level. In separate experiments we measured O 2 consumption and CO 2 production and calculated the Nonshivering Thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and Nonshivering Thermogenesis were lower in animals housed at thermoneutrality (29°C) than in mice housed at 22°. Among mice maintained at 22°C, but not at thermoneutrality, aged animals had greater Nonshivering Thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22°C, showed the changes in Nonshivering Thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.
Jan Nedergaard - One of the best experts on this subject based on the ideXlab platform.
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Nonshivering Thermogenesis and its adequate measurement in metabolic studies.
The Journal of experimental biology, 2011Co-Authors: Barbara Cannon, Jan NedergaardAbstract:Alterations in Nonshivering Thermogenesis are presently discussed as being both potentially causative of and able to counteract obesity. However, the necessity for mammals to defend their body temperature means that the ambient temperature profoundly affects the outcome and interpretation of metabolic experiments. An adequate understanding and assessment of Nonshivering Thermogenesis is therefore paramount for metabolic studies. Classical Nonshivering Thermogenesis is facultative, i.e. it is only activated when an animal acutely requires extra heat (switched on in minutes), and adaptive, i.e. it takes weeks for an increase in capacity to develop. Nonshivering Thermogenesis is fully due to brown adipose tissue activity; adaptation corresponds to the recruitment of this tissue. Diet-induced Thermogenesis is probably also facultative and adaptive and due to brown adipose tissue activity. Although all mammals respond to injected/infused norepinephrine (noradrenaline) with an increase in metabolism, in non-adapted mammals this increase mainly represents the response of organs not involved in Nonshivering Thermogenesis; only the increase after adaptation represents Nonshivering Thermogenesis. Thermogenesis (metabolism) should be expressed per animal, and not per body mass [not even to any power (0.75 or 0.66)]. A 'cold tolerance test' does not examine Nonshivering Thermogenesis capacity; rather it tests shivering capacity and endurance. For mice, normal animal house temperatures are markedly below thermoneutrality, and the mice therefore have a metabolic rate and food consumption about 1.5 times higher than their intrinsic requirements. Housing and examining mice at normal house temperatures carries a high risk of identifying false positives for intrinsic metabolic changes; in particular, mutations/treatments that affect the animal's insulation (fur, skin) may lead to such problems. Correspondingly, true alterations in intrinsic metabolic rate remain undetected when metabolism is examined at temperatures below thermoneutrality. Thus, experiments with animals kept and examined at thermoneutrality are likely to yield an improved possibility of identifying agents and genes important for human energy balance.
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Caveolin-1-ablated mice survive cold by Nonshivering Thermogenesis, despite desensitized adrenergic receptors
2010Co-Authors: Charlotte L. Mattsson, Jan Nedergaard, Robert I. Csikasz, Irina G. Shabalina, Barbara CannonAbstract:Caveolin-1-ablated mice survive cold by Nonshivering Thermogenesis, despite desensitized adrenergic receptors
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Nonshivering Thermogenesis protects against defective calcium handling in muscle
The FASEB Journal, 2008Co-Authors: Jan Aydin, Barbara Cannon, Jan Nedergaard, Irina G. Shabalina, Nicolas Place, Steven Reiken, Shi-jin Zhang, Andrew M. Bellinger, Andrew R. Marks, Joseph D. BrutonAbstract:When acutely exposed to a cold environment, mammals shiver to generate heat. During prolonged cold exposure, shivering is replaced by adaptive adrenergic Nonshivering Thermogenesis with increased heat production in brown adipose tissue due to activation of uncoupling protein-1 (UCP1). This cold acclimation is associated with chronically increased sympathetic stimulation of skeletal muscle, which may increase the sarcoplasmic reticulum (SR) Ca(2+) leak via destabilized ryanodine receptor 1 (RyR1) channel complexes. Here, we use genetically engineered UCP1-deficient (UCP1-KO) mice that rely completely on shivering in the cold. We examine soleus muscle, which participates in shivering, and flexor digitorum brevis (FDB) muscle, a distal and superficial muscle that does not shiver. Soleus muscles of cold-acclimated UCP1-KO mice exhibited severe RyR1 PKA hyperphosphorylation and calstabin1 depletion, as well as markedly decreased SR Ca(2+) release and force during contractions. In stark contrast, the RyR1 channel complexes were little affected, and Ca(2+) and force were not decreased in FDB muscles of cold-acclimated UCP1-KO mice. These results indicate that activation of UCP1-mediated heat production in brown adipose tissue during cold exposure reduces the necessity for shivering and thus prevents the development of severe dysfunction in shivering muscles.
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UCP1 is essential for adaptive adrenergic Nonshivering Thermogenesis
American Journal of Physiology-Endocrinology and Metabolism, 2006Co-Authors: Valeria Golozoubova, Barbara Cannon, Jan NedergaardAbstract:Participation of brown adipose tissue [through the action of the uncoupling protein-1 (UCP1)] in adaptive adrenergic Nonshivering Thermogenesis is recognized, but the existence of a response to adr...
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Only UCP1 can mediate adaptive Nonshivering Thermogenesis in the cold
The FASEB Journal, 2001Co-Authors: Valeria Golozoubova, Barbara Cannon, Esa Hohtola, Anita Matthias, Anders Jacobsson, Jan NedergaardAbstract:Adaptive Nonshivering Thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive Nonshivering Thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive Nonshivering Thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4C during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive Nonshivering Thermogenesis, however, no substitution of shivering by any adaptive Nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive Nonshivering Thermogenesis has recurrently been implied, we did not find any indication of such Thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive Nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive Nonshivering Thermogenesis in the cold.
Barbara Cannon - One of the best experts on this subject based on the ideXlab platform.
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Nonshivering Thermogenesis and its adequate measurement in metabolic studies.
The Journal of experimental biology, 2011Co-Authors: Barbara Cannon, Jan NedergaardAbstract:Alterations in Nonshivering Thermogenesis are presently discussed as being both potentially causative of and able to counteract obesity. However, the necessity for mammals to defend their body temperature means that the ambient temperature profoundly affects the outcome and interpretation of metabolic experiments. An adequate understanding and assessment of Nonshivering Thermogenesis is therefore paramount for metabolic studies. Classical Nonshivering Thermogenesis is facultative, i.e. it is only activated when an animal acutely requires extra heat (switched on in minutes), and adaptive, i.e. it takes weeks for an increase in capacity to develop. Nonshivering Thermogenesis is fully due to brown adipose tissue activity; adaptation corresponds to the recruitment of this tissue. Diet-induced Thermogenesis is probably also facultative and adaptive and due to brown adipose tissue activity. Although all mammals respond to injected/infused norepinephrine (noradrenaline) with an increase in metabolism, in non-adapted mammals this increase mainly represents the response of organs not involved in Nonshivering Thermogenesis; only the increase after adaptation represents Nonshivering Thermogenesis. Thermogenesis (metabolism) should be expressed per animal, and not per body mass [not even to any power (0.75 or 0.66)]. A 'cold tolerance test' does not examine Nonshivering Thermogenesis capacity; rather it tests shivering capacity and endurance. For mice, normal animal house temperatures are markedly below thermoneutrality, and the mice therefore have a metabolic rate and food consumption about 1.5 times higher than their intrinsic requirements. Housing and examining mice at normal house temperatures carries a high risk of identifying false positives for intrinsic metabolic changes; in particular, mutations/treatments that affect the animal's insulation (fur, skin) may lead to such problems. Correspondingly, true alterations in intrinsic metabolic rate remain undetected when metabolism is examined at temperatures below thermoneutrality. Thus, experiments with animals kept and examined at thermoneutrality are likely to yield an improved possibility of identifying agents and genes important for human energy balance.
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Caveolin-1-ablated mice survive cold by Nonshivering Thermogenesis, despite desensitized adrenergic receptors
2010Co-Authors: Charlotte L. Mattsson, Jan Nedergaard, Robert I. Csikasz, Irina G. Shabalina, Barbara CannonAbstract:Caveolin-1-ablated mice survive cold by Nonshivering Thermogenesis, despite desensitized adrenergic receptors
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Nonshivering Thermogenesis protects against defective calcium handling in muscle
The FASEB Journal, 2008Co-Authors: Jan Aydin, Barbara Cannon, Jan Nedergaard, Irina G. Shabalina, Nicolas Place, Steven Reiken, Shi-jin Zhang, Andrew M. Bellinger, Andrew R. Marks, Joseph D. BrutonAbstract:When acutely exposed to a cold environment, mammals shiver to generate heat. During prolonged cold exposure, shivering is replaced by adaptive adrenergic Nonshivering Thermogenesis with increased heat production in brown adipose tissue due to activation of uncoupling protein-1 (UCP1). This cold acclimation is associated with chronically increased sympathetic stimulation of skeletal muscle, which may increase the sarcoplasmic reticulum (SR) Ca(2+) leak via destabilized ryanodine receptor 1 (RyR1) channel complexes. Here, we use genetically engineered UCP1-deficient (UCP1-KO) mice that rely completely on shivering in the cold. We examine soleus muscle, which participates in shivering, and flexor digitorum brevis (FDB) muscle, a distal and superficial muscle that does not shiver. Soleus muscles of cold-acclimated UCP1-KO mice exhibited severe RyR1 PKA hyperphosphorylation and calstabin1 depletion, as well as markedly decreased SR Ca(2+) release and force during contractions. In stark contrast, the RyR1 channel complexes were little affected, and Ca(2+) and force were not decreased in FDB muscles of cold-acclimated UCP1-KO mice. These results indicate that activation of UCP1-mediated heat production in brown adipose tissue during cold exposure reduces the necessity for shivering and thus prevents the development of severe dysfunction in shivering muscles.
-
UCP1 is essential for adaptive adrenergic Nonshivering Thermogenesis
American Journal of Physiology-Endocrinology and Metabolism, 2006Co-Authors: Valeria Golozoubova, Barbara Cannon, Jan NedergaardAbstract:Participation of brown adipose tissue [through the action of the uncoupling protein-1 (UCP1)] in adaptive adrenergic Nonshivering Thermogenesis is recognized, but the existence of a response to adr...
-
Only UCP1 can mediate adaptive Nonshivering Thermogenesis in the cold
The FASEB Journal, 2001Co-Authors: Valeria Golozoubova, Barbara Cannon, Esa Hohtola, Anita Matthias, Anders Jacobsson, Jan NedergaardAbstract:Adaptive Nonshivering Thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive Nonshivering Thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive Nonshivering Thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4C during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive Nonshivering Thermogenesis, however, no substitution of shivering by any adaptive Nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive Nonshivering Thermogenesis has recurrently been implied, we did not find any indication of such Thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive Nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive Nonshivering Thermogenesis in the cold.
Nadejda A. Kosheleva - One of the best experts on this subject based on the ideXlab platform.
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Nonshivering Thermogenesis in adult and aged c57bl 6j mice housed at 22 c and at 29 c
Experimental Gerontology, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Nadejda A. KoshelevaAbstract:Abstract Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22°C or at thermoneutrality (29°C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5°C below control level. In separate experiments we measured O 2 consumption and CO 2 production and calculated the Nonshivering Thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and Nonshivering Thermogenesis were lower in animals housed at thermoneutrality (29°C) than in mice housed at 22°. Among mice maintained at 22°C, but not at thermoneutrality, aged animals had greater Nonshivering Thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22°C, showed the changes in Nonshivering Thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.
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cold acclimation associated changes in brown adipose tissue do not necessarily indicate an increase of Nonshivering Thermogenesis in c57bl 6j mice
Physiology & Behavior, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Lori A Clow, Nadejda A. KoshelevaAbstract:We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of Nonshivering Thermogenesis. To understand the origin of this failure, this study was intended to measure Nonshivering Thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint at 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cold acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system.
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Nonshivering Thermogenesis in adult and aged C57BL/6J mice housed at 22°C and at 29°C
Experimental Gerontology, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Nadejda A. KoshelevaAbstract:Abstract Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22°C or at thermoneutrality (29°C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5°C below control level. In separate experiments we measured O 2 consumption and CO 2 production and calculated the Nonshivering Thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and Nonshivering Thermogenesis were lower in animals housed at thermoneutrality (29°C) than in mice housed at 22°. Among mice maintained at 22°C, but not at thermoneutrality, aged animals had greater Nonshivering Thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22°C, showed the changes in Nonshivering Thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.
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Cold Acclimation-Associated Changes in Brown Adipose Tissue do Not Necessarily Indicate an Increase of Nonshivering Thermogenesis in C57BL/6J Mice
Physiology & Behavior, 1996Co-Authors: Mark I. Talan, Sergey A. Kirov, Lori A Clow, Nadejda A. KoshelevaAbstract:We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of Nonshivering Thermogenesis. To understand the origin of this failure, this study was intended to measure Nonshivering Thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint at 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cold acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system.
Tore Bengtsson - One of the best experts on this subject based on the ideXlab platform.
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β₁-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β₃-adrenergic receptor-knockout mice via Nonshivering Thermogenesis.
AJP - Endocrinology and Metabolism, 2011Co-Authors: Charlotte L. Mattsson, Robert I. Csikasz, Ekaterina Chernogubova, Daniel L Yamamoto, Helena T Hogberg, Ez-zoubir Amri, Dana S Hutchinson, Tore BengtssonAbstract:With the finding that brown adipose tissue is present and negatively correlated to obesity in adult man, finding the mechanism(s) of how to activate brown adipose tissue in humans could be important in combating obesity, type 2 diabetes, and their complications. In mice, the main regulator of Nonshivering Thermogenesis in brown adipose tissue is norepinephrine acting predominantly via β(3)-adrenergic receptors. However, vast majorities of β(3)-adrenergic agonists have so far not been able to stimulate human β(3)-adrenergic receptors or brown adipose tissue activity, and it was postulated that human brown adipose tissue could be regulated instead by β(1)-adrenergic receptors. Therefore, we have investigated the signaling pathways, specifically pathways to Nonshivering Thermogenesis, in mice lacking β(3)-adrenergic receptors. Wild-type and β(3)-knockout mice were either exposed to acute cold (up to 12 h) or acclimated for 7 wk to cold, and parameters related to metabolism and brown adipose tissue function were investigated. β(3)-knockout mice were able to survive both acute and prolonged cold exposure due to activation of β(1)-adrenergic receptors. Thus, in the absence of β(3)-adrenergic receptors, β(1)-adrenergic receptors are effectively able to signal via cAMP to elicit cAMP-mediated responses and to recruit and activate brown adipose tissue. In addition, we found that in human multipotent adipose-derived stem cells differentiated into functional brown adipocytes, activation of either β(1)-adrenergic receptors or β(3)-adrenergic receptors was able to increase UCP1 mRNA and protein levels. Thus, in humans, β(1)-adrenergic receptors could play an important role in regulating Nonshivering Thermogenesis.
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β1-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β3-adrenergic receptor-knockout mice via Nonshivering Thermogenesis
American Journal of Physiology-Endocrinology and Metabolism, 2011Co-Authors: Charlotte L. Mattsson, Robert I. Csikasz, Ekaterina Chernogubova, Daniel L Yamamoto, Helena T Hogberg, Ez-zoubir Amri, Dana S Hutchinson, Tore BengtssonAbstract:With the finding that brown adipose tissue is present and negatively correlated to obesity in adult man, finding the mechanism(s) of how to activate brown adipose tissue in humans could be important in combating obesity, type 2 diabetes, and their complications. In mice, the main regulator of Nonshivering Thermogenesis in brown adipose tissue is norepinephrine acting predominantly via β(3)-adrenergic receptors. However, vast majorities of β(3)-adrenergic agonists have so far not been able to stimulate human β(3)-adrenergic receptors or brown adipose tissue activity, and it was postulated that human brown adipose tissue could be regulated instead by β(1)-adrenergic receptors. Therefore, we have investigated the signaling pathways, specifically pathways to Nonshivering Thermogenesis, in mice lacking β(3)-adrenergic receptors. Wild-type and β(3)-knockout mice were either exposed to acute cold (up to 12 h) or acclimated for 7 wk to cold, and parameters related to metabolism and brown adipose tissue function were investigated. β(3)-knockout mice were able to survive both acute and prolonged cold exposure due to activation of β(1)-adrenergic receptors. Thus, in the absence of β(3)-adrenergic receptors, β(1)-adrenergic receptors are effectively able to signal via cAMP to elicit cAMP-mediated responses and to recruit and activate brown adipose tissue. In addition, we found that in human multipotent adipose-derived stem cells differentiated into functional brown adipocytes, activation of either β(1)-adrenergic receptors or β(3)-adrenergic receptors was able to increase UCP1 mRNA and protein levels. Thus, in humans, β(1)-adrenergic receptors could play an important role in regulating Nonshivering Thermogenesis.
