Changes in the Amount and Properties of Adenyl Cyclase in Brown Adipose Tissue during Acclimation of Rats to Cold

1971 ◽  
Vol 49 (7) ◽  
pp. 802-810 ◽  
Author(s):  
Michelle Muirhead ◽  
Jean Himms-Hagen

Adenyl cyclase of interscapular brown adipose tissue of rats undergoing acclimation to cold was measured in order to find out whether the amount of the nor adrenaline-stimulated enzyme might be increased in cold-acclimated rats, in which a characteristic large increase in the overall calorigenic response to noradrenaline (nonshivering thermogenesis) is induced by the prolonged exposure to cold (4–8 weeks). It was found that the growth of the brown adipose tissue in the acclimating rats is accompanied by an increase in the total amount of noradrenaline-stimulated adenyl cyclase activity. Since this increase does not keep pace with the growth of the tissue a reduction in specific activity of the noradrenaline-stimulated adenyl cyclase was observed. Thus no evidence was obtained for an increased concentration of noradrenaline-responsive structures in the cell membrane of the brown adipose tissue of cold-acclimated rats.In contrast, fluoride-stimulated adenyl cyclase activity increased almost twofold after only 2 days of exposure to cold and before the growth of the tissue had started. Thereafter the activity of this enzyme increased in parallel to the growth of the tissue. The extra activity that developed during the first 2 days persisted throughout the period of acclimation to cold (8 weeks); it disappeared within 1 day when the cold-acclimated rats were returned to room temperature.These changes in adenyl cyclase activity are more rapid than any hitherto reported. They presumably reflected a change in the properties of the cell membrane in response to an environmental stress. It is not known whether the increase in measurable fluoride-stimulated adenyl cyclase activity reflects an increase in the synthesis of a specific protein or an unmasking of the activity of an enzyme already present.No change in the specific activity of cyclic AMP phosphodiesterase was observed; during acclimation to cold the total amount of this enzyme increased in parallel with the growth of the tissue.

1977 ◽  
Vol 55 (6) ◽  
pp. 1242-1245 ◽  
Author(s):  
Thierry Cresteil

An adenyl cyclase activity was measurable in the brown adipose tissue of fetal rat, and could be stimulated in vitro by noradrenaline during the last 3 days of fetal life. The stimulating effect of noradrenaline was maximal at birth and decreased during the first days of extrauterine life.Ingestion by mothers of a high lipid diet modified the developmental pattern of fetal adenyl cyclase. The linoleic acid content of mother's diet had no effect on the noradrenaline- or fluoride-stimulated specific activities except on the day 22 of gestation. Relative noradrenaline-stimulated activity, expressed as a fraction of the maximal activity, was significantly increased in fetuses and 1-day-old newborns from mothers fed a high linoleic acid diet, but no effect was observed in suckling newborns.


1980 ◽  
Vol 239 (1) ◽  
pp. C18-C22 ◽  
Author(s):  
J. Himms-Hagen ◽  
C. Gwilliam

The size (wet weight, total protein, total cytochrome oxidase) of interscapular brown adipose tissue is reduced to about one-half of normal in the cardiomyopathic hamster (BIO 14.6). The mitochondria are normal in binding of purine nucleotides [guanosine 5'-diphosphate (GDP)] and in proportion of polypeptides in the region of 32,000, both indices of the thermogenic proton conductance pathway, and in specific activity of cytochrome oxidase. Brown adipose tissue of the cardiomyopathic hamster can grow during acclimation to 4 degrees C, but its size remains smaller than in cold-acclimated normal hamsters. Mitochondrial polypeptide composition is not altered by acclimation to cold, but a large increase in mitochondrial GDP binding occurs in both normal and cardiomyopathic hamsters. The reduced calorigenic response of cardiomyopathic hamsters to catecholamines (Horwitz, B.A., and G.E. Hanes, Proc. Soc. Exp. Biol. Med. 147: 393-395, 1974) may, at least in part, be explained by a reduction in the amount of brown adipose tissue, the major site of this response. A defect in control of growth of this tissue in the cardiomyopathic hamster is suggested.


1991 ◽  
Vol 277 (3) ◽  
pp. 665-669 ◽  
Author(s):  
J R D Mitchell ◽  
E D Saggerson

1. Measurements were made, relative to tissue DNA, of the activities of enzymes of glycerolipid synthesis in homogenates of interscapular brown adipose tissue. These were: mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), Mg(2+)-dependent phosphatidate phosphohydrolase (PPH) and fatty acyl-CoA synthetase (FAS). 2. In normal animals, 3 days of cold-exposure (4 degrees C) increased all activities. The increase in mitochondrial GPAT activity was particularly pronounced (5-fold). Administration of the beta-adrenergic agonist BRL 26830A mimicked the effect of cold on microsomal GPAT activity. Mitochondrial GPAT, PPH and FAS activities were unresponsive to BRL 26830A. The alpha-adrenergic agonist phenylephrine significantly decreased activities of GPAT and PPH. 3. Streptozotocin-diabetes decreased mitochondrial GPAT activity, but did not abolish the effect of cold to increase this activity or the activity of microsomal GPAT. Diabetes abolished the effect of cold on PPH and FAS activities. 4. The findings are relevant to signals that drive early events in mitochondriogenesis and cell proliferation in brown adipose tissue on exposure to cold.


1969 ◽  
Vol 47 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Jean Himms-Hagen

The effect of exposure to cold (4°) on the incorporation of glucose carbon into total lipids of interscapular brown adipose tissue was studied in warm-acclimated and cold-acclimated rats of different ages. Exposure to cold had little effect on the very low incorporation in warm-acclimated rats regardless of their ages. Incorporation was always greater in cold-acclimated rats in the cold than in warm-acclimated rats in the cold, but the increase due to cold exposure was smaller in young cold-acclimated rats than in older cold-acclimated rats. The concentration of glucose in the blood was highest in the youngest rats and was increased further after exposure to cold; older rats did not become hyperglycemic in the cold. The relation between brown adipose tissue metabolism and nonshivering thermogenesis is discussed.


1992 ◽  
Vol 282 (1) ◽  
pp. 231-235 ◽  
Author(s):  
D M Smith ◽  
S R Bloom ◽  
M C Sugden ◽  
M J Holness

Starvation (48 h) decreased the concentration of mRNA of the insulin-responsive glucose transporter isoform (GLUT 4) in interscapular brown adipose tissue (IBAT) (56%) and tibialis anterior (10%). Despite dramatic [7-fold (tibialis anterior) and 40-fold (IBAT)] increases in glucose utilization after 2 and 4 h of chow re-feeding, no significant changes in GLUT 4 mRNA concentration were observed in these tissues over this re-feeding period. The results exclude changes in GLUT 4 mRNA concentration in mediating the responses of glucose transport in these tissues to acute re-feeding after prolonged starvation.


1991 ◽  
Vol 277 (3) ◽  
pp. 625-629 ◽  
Author(s):  
J P Revelli ◽  
R Pescini ◽  
P Muzzin ◽  
J Seydoux ◽  
M G Fitzgerald ◽  
...  

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Van Schaik ◽  
C. Kettle ◽  
R. Green ◽  
W. Sievers ◽  
M. W. Hale ◽  
...  

AbstractThe role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.


Author(s):  
Clara Huesing ◽  
Rui Zhang ◽  
Sanjeev Gummadi ◽  
Nathan Lee ◽  
Emily Qualls‐Creekmore ◽  
...  

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