RESUMEN
The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Frío , Proteínas de Choque Térmico/metabolismo , Tejido Adiposo Pardo/citología , Animales , Secuencia de Bases , Proteínas Portadoras/genética , ADN/metabolismo , Proteínas del Choque Térmico HSP72 , Proteínas de Choque Térmico/genética , Canales Iónicos , Cinética , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos ICR , Proteínas Mitocondriales , Datos de Secuencia Molecular , Sondas de Oligonucleótidos/genética , ARN Mensajero/metabolismo , Receptores Adrenérgicos/fisiología , Factores de Transcripción/metabolismo , Proteína Desacopladora 1RESUMEN
Adult and aged male C57BL/6J mice were subjected to a 3-h cold stress test at either 24 degrees C, 18 degrees C, 12 degrees C, or 6 degrees C. Body mass was measured before the test, and colonic temperature, O2 consumption, and CO2 production were measured during the test. The slopes of colonic temperature over time of test and the mean metabolic heat production were calculated for each animal. While adult mice had a relatively small reduction in colonic temperature during the test at all four ambient temperatures, in the aged mice ambient temperatures resulted in steeper reductions of colonic temperature. In adult mice, an increase in metabolic heat production was proportional to ambient cold. The thermogenic response of aged mice at 24 degrees C and at 18 degrees C was similar to adult mice, suggesting that the ability of aged mice to respond to cold by increasing heat production does not diminish with age. However, in aged mice metabolic heat production at 12 degrees C and 6 degrees C was significantly below that of adult mice, which indicated a reduced capacity for thermogenesis.
Asunto(s)
Envejecimiento/fisiología , Regulación de la Temperatura Corporal , Animales , Frío , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Nine-month-old male C57BL/6J mice were subjected to three-hour cold stress tests (partial restraint at 6 degrees C) at 9:00 a.m. or at 1:00 p.m. Tests were repeated three times at two-week intervals at the same time of day. Body temperature was measured by colonic thermoprobe, and metabolic heat production was measured by indirect calorimetry during each test. All mice showed habituation to repeated cold exposures (an improvement of cold tolerance across tests) due to an increase in metabolic heat production. The levels of metabolic heat production were similar during morning and afternoon testing; however, mice tested in the afternoon had consistently poorer cold tolerance, which indicated increased heat loss. Increased heat loss in mice of similar body weight and presumably similar body composition, suggests that there is less effective cold-induced skin vasoconstriction during the afternoon. We hypothesize that the compromised skin vasomotor response during the afternoon cold exposure results from competing effects of vasodilation due to local autoregulation stimulated by a circadian reduction of cardiac output during the sleep phase, and vasoconstriction due to the cold stress.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Ritmo Circadiano/fisiología , Frío , Animales , Peso Corporal/fisiología , Habituación Psicofisiológica/fisiología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Adult and aged male C57BL/6J mice were subjected to three consecutive 3-hour cold stress tests (partial physical restraint at 6 degrees C), repeated 2 weeks apart. Body mass and colonic temperature were measured before each test, and colonic temperature, O2 consumption, and CO2 production were measured during cold exposure. The slopes of colonic temperature and heat production and the mean metabolic heat production were calculated for each animal. Adult mice showed stronger cold tolerance compared to aged mice and also exhibited habituation to cold exposure (improvement of cold tolerance with repeated tests). Mean metabolic heat production during cold exposure was greater in adult mice, and only adults demonstrated significant increases across tests in both metabolic heat production and slope of metabolic heat production over time. We hypothesize that reduced cold tolerance in aged mice is related mainly to a decrease in metabolic heat production. Increased metabolic heat production in subsequent tests in adults is a probable mechanism for habituation to repeated cold exposure.
Asunto(s)
Envejecimiento/fisiología , Regulación de la Temperatura Corporal , Frío , Animales , Peso Corporal , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Adult (9-14 month) and aged (29-31 month) male C57BL/6J mice were subjected to 3 baseline tests (BASE), 3 cold tests (COLD), or 3 baseline immediately followed by cold tests (BASE/COLD). All tests consisted of partial restraint, and baseline tests were at 24 degrees C for 1 h while cold tests were at 6 degrees C for 3 h. All tests were started at 0900 and were repeated every 2 weeks. Mice were weighed before each test and colonic temperature, O2 consumption, and CO2 production were measured every 4 min for the duration of the test. Mean metabolic heat production during baseline and/or cold and slopes of colonic temperature over time during cold were calculated for each animal. Metabolic heat production at 24 degrees C in both BASE and BASE/COLD was the same in aged mice as adults, however, at degrees C BASE/COLD adult mice increased metabolic heat production compared to 24 degrees C, while aged mice produced a similar amount of heat at both 6 degrees C and 24 degrees C. When comparing metabolic heat production at 6 degrees C between COLD and BASE/COLD mice, adult COLD mice demonstrate an habituation to repeated cold exposure accompanied by increasing heat production, while BASE/COLD adults produce higher heat in all 3 cold exposures. The authors suggest that this is due to a priming of heat production in adults by restraint before the cold. In aged mice, neither COLD nor BASE/COLD groups demonstrate habituation, but BASE/COLD mice produce more heat than COLD during cold exposure, again indicating baseline priming of heat production. The data imply that aged mice have an impairment in specific cold-induced thermogenesis, while their abilities to produce heat in response to restraint-induced sympathetic activation remains intact.