Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we report the development of the immunologically detected uncoupling protein (UCP) in brown adipose tissue during the perinatal period in the rat and its relationship with its functional activity expressed in terms of GDP-binding capacity, GDP-sensitive permeabilities and GDP-sensitive respiration. Immunologically detected UCP increased during the last 2 days of foetal life (under euthermic conditions) and after birth (after postnatal hypothermia) during the early suckling period, reaching its maximum value on day 10 after birth. This increase in UCP is accompanied by parallel increases in the GDP-binding capacity, GDP-sensitive permeabilities to protons and chloride ions and GDP-inhibitable respiration. During the suckling--weaning transition, there was a regression of the parameters related to the functional activity of the UCP (GDP-binding capacity and nucleotide-sensitive permeabilities and respiration) without changes in the immunologically detected UCP. These results suggest that the involution of this tissue in the rat commences in this period; the first parameters affected are those related to the functional activity of the UCP while the UCP is still present in its highest level. This seems to support the idea that, in this period of development of the rat, the UCP may exist in the brown fat mitochondria in a functional (unmasked) form and a non-functional (masked) form.
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PMID:Development of the uncoupling protein in the rat brown-adipose tissue during the perinatal period. Its relationship with the mitochondrial GDP-binding and GDP-sensitive ion permeabilities and respiration. 168 44

The effect of thyroxine (T4) and triiodothyronine (T3) on the expression of uncoupling protein (UCP) in rat brown adipose tissue (BAT) has been examined. Thyroidectomized rats have a threefold reduction in basal UCP levels. When exposed to cold, they become hypothermic and show a fivefold lower response of UCP than euthyroid controls. T3 augments the basal levels and the response of UCP and its mRNA to cold in a dose-dependent manner. However, to normalize the response of UCP, T3 has to be given in a dosage that produces systemic hyperthyroidism. Mere T3 replacement corrects the systemic hypothyroidism but not the hypothermia or the low levels of UCP. In contrast, replacement doses of T4 prevent the hypothermia and correct the UCP level. Both effects of T4 are blocked by preventing T4 to T3 conversion in BAT. Thus, the optimal UCP response to cold and protection against hypothermia require a high BAT T3 concentration, which is attained from euthyroid levels of T4 via the activation of the BAT T4 5'deiodinase during cold exposure, but not from euthyroid plasma T3 levels.
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PMID:Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. 379 28

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue beta-guanidinopropionic acid (beta-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of beta-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in beta-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of beta-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of beta-GPA rats was significantly lower than that in control rats (the relative amounts were 77 +/- 6 and 100 +/- 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in beta-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in beta-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of beta-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.
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PMID:Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed beta-guanidinopropionic acid. 761 43

To investigate whether attenuation of thermogenesis in interscapular brown adipose tissue (IBAT) may account for the loss of thermoregulation with age, we examined two indices of thermogenesis after two types of cold exposure: one in which the senescent rats maintained homeothermy and the other in which the senescent rats became hypothermic. To this end, we assessed body temperature, guanosine 5'-diphosphate (GDP) binding to the IBAT mitochondrial uncoupling protein (UCP) and the induction of UCP mRNA after both 1-hr and 48-hr mild cold exposures at 8 degrees C and after a more severe, 1-hr cold exposure at 4 degrees C in 3- and 24-month-old F-344 rats. Thermoneutrality was determined to occur at an ambient temperature of 26 degrees C in rats of both ages. In the 1-hr mild cold-exposed rats, there was no significant increase in GDP binding to IBAT UCP. However, after 48 hr of mild cold exposure, there was a 3-fold increase in GDP binding and a 5-fold increase in the expression of UCP mRNA despite no hypothermia in either the young or old rats. During the more severe cold exposure, the senescent rats, but not the young rats, became hypothermic. GDP binding to UCP increased 75% following cold exposure and, surprisingly was the same in young and old rats. UCP transcripts did not increase during the 1-hr cold exposure. These data, coupled with our previous findings of diminished beta 3-agonist-stimulated IBAT thermogenesis, suggest that (i) IBAT thermogenesis, at least in the senescent rats, may be mediated by other than beta 3-adrenergic receptors, and (ii) that altered heat dissipation or impaired thermogenesis at some site other than interscapular BAT is responsible for the observed hypothermia.
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PMID:Thermoregulation with age: role of thermogenesis and uncoupling protein expression in brown adipose tissue. 810 65

The effect of fetal thyroidectomy on thermoregulation in newborn lambs was investigated. Seven of 14 lambs born normally at term were thyroidectomized at Day 127 of gestation. Colonic temperature and oxygen consumption were measured during non-rapid eye movement sleep 6-45 h after birth. All lambs were then killed and perirenal brown adipose tissue was sampled for measurement of thermogenic activity (guanosine diphosphate binding), uncoupling protein and lipid contents. Thyroidectomized lambs tended to have a mean colonic temperature 2.35 degrees C lower (P = 0.067) than controls and two became hypothermic (i.e. colonic temperature < 35 degrees C). Thyroidectomized lambs exhibited lower rates of oxygen consumption (P = 0.05) and an increased incidence of shivering thermogenesis. The perirenal adipose tissue of these lambs had a lower thermogenic activity (P < 0.01), less uncoupling protein (P < 0.01) and higher lipid content (P = 0.072) compared with intact controls. It is concluded that fetal thyroidectomy results in a decreased ability of newborn lambs to utilize nonshivering thermogenesis in brown adipose tissue as well as increasing the incidence of hypothermia. These changes are associated with decreased synthesis of uncoupling protein and functional development of brown adipose tissue in the late gestation fetus.
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PMID:Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs. 889 35

We previously showed that, although cold-induced thermoregulation is attenuated in 26-mo-old male Fischer 344 (F344) rats, not all rats this age exhibit the same degree of cold-exposed hypothermia or diminished brown adipose tissue nonshivering thermogenic capacity. Examination of this heterogeneity suggested the hypothesis that it was associated with a difference in the physiological state between aged rats that were maintaining stable body weight versus those showing the rapid weight loss often occurring near the end of the rat's natural life span. To test this, we acutely exposed male F344 rats to cold (4 h at 6 degrees C) beginning at 24 mo of age. This exposure was weekly for the first 2 wk and then on alternate weeks as long as the rat's body weight was stable. If body weight progressively declined for 3-5 consecutive days, the rat's response to the acute cold exposure was again measured, as was that of two additional rats not displaying this rapid loss in body weight. If body temperature decreased during the cold exposure to intraperitoneal temperatures < or = 32.5 degrees C, the rat was killed with pentobarbital sodium and interscapular brown adipose tissue was removed. One of the age-matched controls was also killed at this time. The age at which body weight showed a spontaneous rapid decline ranged from 24.5 to 29 mos. All eight rats displaying spontaneous rapid weight loss had significant hypothermia during the acute cold exposure, whereas none of the eight weight-stable rats did. The development of hypothermia in the spontaneous rapid weight loss group was not, in general, observed before their weight loss. The weight loss and hypothermia were associated with lower levels of brown fat uncoupling protein and significant changes in body fat and protein. These data suggest that the development of senescence-related hypothermia occurs rapidly and is not a simple function of chronological age or the median life span of the animals. Furthermore, these data imply that the rate of aging in terms of maintenance of thermoregulatory homeostasis has both a gradual and rapid component, the latter being associated with a different physiological state than the former.
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PMID:Relationship between cold-induced thermoregulation and spontaneous rapid body weight loss of aging F344 rats. 894 43

Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4 degrees C for 21 days weighed 14% less than controls maintained at 22 degrees C (P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter (P < 0.001). Increase BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.
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PMID:Hyperphagia in cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY. 945 99

In the lamb, the uncoupling protein-1 (UCP1) content of perirenal adipose tissue at birth is an important factor in heat production by non-shivering thermogenesis and the prevention of hypothermia. This study examines UCP1 gene expression and protein content in perirenal adipose tissue over the first 15 days of life by in situ hybridisation and immunohistochemistry. UCP1 mRNA was detected at birth in 30% of adipocytes, and in approximately 24% of fat cells at 2 days of life. However, by 5 days of age and thereafter UCP1 mRNA was undetectable. Immunoreactive UCP1 was present in all adipocytes at birth and at 2 days of age, and remained detectable in a decreasing proportion of cells until day 10 of life. By 15 days of age no immunoreactive UCP1 was detected and the perirenal adipose tissue had the appearance of white fat. It is concluded that UCP1 gene expression is suppressed in most adipocytes in perirenal adipose tissue of newborn lambs, and gene expression rapidly falls in the remaining adipocytes over the first 5 days of postnatal life. In contrast, immunoreactive UCP1, a characteristic of brown adipose tissue, was present in many adipocytes for up to 10 days of age, suggesting that UCP1 has a long half-life in lambs. All adipocytes in perirenal adipose tissue of newborn lambs appear to be functionally brown, but over the first 2 weeks of postnatal life there is a complete transformation to white adipocytes.
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PMID:An immunohistochemical and in situ hybridisation study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue. 979 63

Linking tissue uncoupling protein (UCP) homolog abundance with functional metabolic outcomes and with expression of putative genetic regulators promises to better clarify UCP homolog physiological function. A murine endotoxemia model characterized by marked alterations in thermoregulation was employed to examine the association between heat production, UCP homolog expression, and mitochondrial proton leak ("uncoupling"). After intraperitoneal lipopolysaccharide (LPS, approximately 6 mg/kg) injection, colonic temperature (T(c)) in adult female C57BL6/J mice dropped to a nadir of approximately 30 degrees C by 8 h, preceded by a four- to fivefold drop in liver UCP2 and UCP5/brain mitochondrial carrier protein 1 mRNA levels, with no change in their hindlimb skeletal muscle (SKM) expression. SKM UCP3 mRNA rose fivefold during development of hypothermia and was correlated with an LPS-induced increase in plasma free fatty acid concentration. UCP2 and UCP5 transcripts recovered about three- to sixfold in both tissues starting at 6-8 h, preceding a recovery of T(c) between 16 and 24 h. SKM UCP3 followed an opposite pattern. Such results are not consistent with an important influence of UCP3 in driving heat production but do not preclude a role for UCP2 or UCP5 in this process. The transcription coactivator PGC-1 displayed a transient LPS-evoked rise (threefold) or drop (two- to fivefold) in SKM and liver expression, respectively. No differences between control and LPS-treated mouse liver or SKM in vitro mitochondrial proton leak were evident at time points corresponding to large differences in UCP homolog expression.
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PMID:Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics. 1091 45

Mitochondrial very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children. Sudden death is common, but the underlying mechanisms are not fully understood. We report on a mouse model of VLCAD deficiency with a phenotype induced by the stresses of fasting and cold, which includes hypoglycemia, hypothermia, and severe bradycardia. The administration of glucose did not rescue the mice under stress conditions, but rewarming alone consistently led to heart rate recovery. Brown adipose tissue (BAT) from the VLCAD-/- mice showed elevated levels of the uncoupling protein isoforms and peroxisome proliferator-activated receptor-alpha. Biochemical assessment of the VLCAD(/- mice BAT showed increased oxygen consumption, attributed to uncoupled respiration in the absence of stress. ADP-stimulated respiration was 23.05 (SD 4.17) and 68.24 (SD 6.3) nmol O2.min(-1).mg mitochondrial protein(-1) for VLCAD+/+ and VLCAD-/- mice, respectively (P < 0.001), and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated respiration was 35.9 (SD 3.6) and 49.3 (SD 9) nmol O2.min(-1).mg mitochondrial protein(-1) for VLCAD+/+ and VLCAD-/- mice, respectively (P < 0.20), but these rates were insufficient to protect them in the cold. We conclude that disturbed mitochondrial bioenergetics in BAT is a critical contributing factor for the cold sensitivity in VLCAD deficiency. Our observations provide insights into the possible mechanisms of stress-induced death in human newborns with abnormal fat metabolism and elucidate targeting of specific substrates for particular metabolic needs.
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PMID:Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase. 1619 75


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