scholarly journals Persistence of the effect of insulin on pyruvate dehydrogenase activity in rat white and brown adipose tissue during the preparation and subsequent incubation of mitochondria

1984 ◽  
Vol 217 (2) ◽  
pp. 441-452 ◽  
Author(s):  
R M Denton ◽  
J G McCormack ◽  
S E Marshall
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Plasma Membranes ◽  
Pyruvate Dehydrogenase Kinase ◽  
Epididymal Adipose Tissue ◽  
Short Term ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Increases in the amount of the active non-phosphorylated form of pyruvate dehydrogenase in rat epididymal adipose tissue, as a result of incubation with insulin, persist not only during the preparation of mitochondria but also during subsequent incubation of coupled mitochondria in the presence of respiratory substrates. No effect on insulin was found if the hormone was added directly to mitochondria in the presence or absence of added plasma membranes. Concentrations of several possible regulators of pyruvate dehydrogenase kinase (ATP, ADP, NADH, NAD+, acetyl-CoA, CoA and potassium) were measured in rat epididymal-adipose-tissue mitochondria incubated under conditions where differences in pyruvate dehydrogenase activity persist as a result of insulin action. No alterations were found, and it is suggested that inhibition of the kinase is not the principal means by which insulin activates pyruvate dehydrogenase. The intramitochondrial concentration of magnesium was also unaffected. Differences in pyruvate dehydrogenase activity in interscapular brown adipose tissue associated with manipulation of plasma insulin concentrations of cold-adapted rats were also shown to persist during the preparation and subsequent incubation of mitochondria in the presence or absence of GDP. It is pointed out that the persistence of the effect of insulin on pyruvate dehydrogenase in incubated mitochondria will facilitate the recognition of the mechanism of this action of the hormone. Evidence that the short-term action of insulin involves an increase in pyruvate dehydrogenase phosphate phosphatase activity rather than inhibition of that of pyruvate dehydrogenase kinase is discussed.

scholarly journals Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat

1980 ◽  
Vol 190 (1) ◽  
pp. 95-105 ◽  
Author(s):  
J G McCormack ◽  
R M Denton
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Isocitrate Dehydrogenase ◽  
Epididymal Adipose Tissue ◽  
Ionophore A23187 ◽  
Mitochondrial Inner Membrane ◽  
Brown Adipose ◽  
Oxoglutarate Dehydrogenase

1. Increasing concentrations of both Ca2+ and Sr2+ (generated by using EGTA buffers) resulted in 4-fold increases in the initial activity of pyruvate dehydrogenase within intact uncoupled mitochondria from rat epididymal adipose tissue incubated in the presence of the ionophore A23187, ATP, Mg2+ and oligomycin. The k0.5 values (concentrations required for half-maximal effects) for Ca2+ and Sr2+ were 0.54 and 7.1 microM respectively. In extracts of the mitochondria, pyruvate dehydrogenase phosphate phosphatase activity was stimulated about 4-fold by Ca2+ and Sr2+, with k0.5 values of 1.08 and 6.4 microM respectively. 2. NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase appeared to be rate-limiting in the oxidation of threo-Ds-isocitrate and oxoglutarate by uncoupled mitochondria from brown adipose tissue of cold-adapted rats. Ca2+ (and Sr2+) diminished the Km for the oxidation of both threo-Ds-isocitrate and oxoglutarate. The kinetic constants for these oxidations were very similar to those obtained for the activities of NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase in extracts of the mitochondria. In particular, the k0.5 values for Ca2+ were all in the range 0.2–1.6 microM and Sr2+ was found to mimic Ca2+, but with k0.5 values about 10 times greater. 3. Overall, the results of this study demonstrate that the activities of pyruvate dehydrogenase, NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase may all be increased by Ca2+ and Sr2+ within intact mitochondria. In all cases the k0.5 values are close to 1 and 10 microM respectively, as found for the separated enzymes. Experiments on brown-adipose-tissue mitochondria incubated in the presence of albumin suggest that it may be possible to use the sensitivity of the dehydrogenases to Ca2+ as a means of assessing the distribution of Ca2+ across the mitochondrial inner membrane.

scholarly journals Modulation in vivo of β-adrenergic-receptor subtypes in rat brown adipose tissue by the thermogenic agonist Ro 16–8714

1992 ◽  
Vol 286 (3) ◽  
pp. 743-746 ◽  
Author(s):  
J P Revelli ◽  
P Muzzin ◽  
J P Giacobino
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Plasma Membranes ◽  
State Level ◽  
Zucker Rats ◽  
Receptor Subtypes ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Beta Adrenergic Agonist

The number of beta 3-adrenergic receptors (AR) in plasma membranes from interscapular brown adipose tissue (IBAT) was decreased by 62% in lean Zucker rats treated with the thermogenic beta-adrenergic agonist Ro 16-8714 as compared with controls after 72 h of treatment. The loss of beta 3-AR number was preceded by a 93% decrease in the steady-state level of beta 3-AR mRNA at 30 h. Similar results were obtained in obese (fa/fa) Zucker rats. Ro 16-8714 had no effect on the number of beta 1- and beta 2-ARs in IBAT. This is the first report to demonstrate that the beta 3-AR in IBAT can be specifically down-regulated in vivo by exposure to a thermogenic agonist.

scholarly journals Evidence that fatty acid synthesis in the interscapular brown adipose tissue of cold-adapted rats is increased in vivo by insulin by mechanisms involving parallel activation of pyruvate dehydrogenase and acetyl-coenzyme A carboxylase

1977 ◽  
Vol 166 (3) ◽  
pp. 627-630 ◽  
Author(s):  
J G McCormack ◽  
R M Denton
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Plasma Insulin ◽  
Acid Synthesis ◽  
Interscapular Brown Adipose Tissue ◽  
Cold Adapted ◽  
Brown Adipose

Plasma insulin concentrations in cold-adapted rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in interscapular brown adipose tissue were determined from the incorporation of 3H from 3H2O into tissue lipid. Rates of synthesis were greatly elevated after glucose administration and markedly decreased after injection with anti-insulin serum. Parallel changes in the initial activities of both acetyl-CoA carboxylase and pyruvate dehydrogenase were observed under these conditions, but no changes in total activities were evident. The results suggest that this tissue is an important site of fatty acid synthesis in the cold-adapted rat and that this feature of the tissue is sensitive to changes in plasma insulin concentrations.

scholarly journals Evidence that noradrenaline increases pyruvate dehydrogenase activity and decreases acetyl-CoA carboxylase activity in rat interscapular brown adipose tissue in vivo

1985 ◽  
Vol 228 (3) ◽  
pp. 751-755 ◽  
Author(s):  
J M Gibbins ◽  
R M Denton ◽  
J G McCormack
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Carboxylase Activity ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

The rate of fatty acid synthesis in interscapular brown adipose tissue of female cold-adapted rats, as measured by the incorporation of 3H from 3H2O into tissue lipid, was decreased by about 70% after injection of noradrenaline. There was a similar decrease in the activity of acetyl-CoA carboxylase. In contrast, the proportion of pyruvate dehydrogenase in its active non-phosphorylated form was greatly increased after injection of noradrenaline. This finding suggests that the oxidation of glucose may be important in noradrenaline-induced thermogenesis in rat brown adipose tissue.

scholarly journals Lipogenesis in interscapular brown adipose tissue of virgin, pregnant and lactating rats. The effects of intragastric feeding

1980 ◽  
Vol 190 (2) ◽  
pp. 477-480 ◽  
Author(s):  
L Agius ◽  
D H Williamson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Insulin Deficiency ◽  
Short Term ◽  
Interscapular Brown Adipose Tissue ◽  
Medium Chain ◽  
Brown Adipose

Lipogenesis in brown adipose tissue of virgin rats increased 8—10-fold after intragastric feeding with glucose or medium-chain triacylglycerol, and this increase was prevented by short-term insulin deficiency. Brown adipose tissue increased in weight during pregnancy, regressed during lactation and hypertrophied again on weaning; the rate of lipogenesis paralleled these changes. Glucose did not increase brown-adipose-tissue lipogenesis at mid-lactation.

scholarly journals Glucose transporter expression and glucose utilization in skeletal muscle and brown adipose tissue during starvation and re-feeding

1992 ◽  
Vol 282 (1) ◽  
pp. 231-235 ◽  
Author(s):  
D M Smith ◽  
S R Bloom ◽  
M C Sugden ◽  
M J Holness
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Tibialis Anterior ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Interscapular Brown Adipose Tissue ◽  
Glut 4 ◽  
Mrna Concentration ◽  
Brown Adipose ◽  
Transporter Expression

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.

scholarly journals Changes in β1- and β2-adrenergic receptor mRNA levels in brown adipose tissue and heart of hypothyroid rats

1991 ◽  
Vol 277 (3) ◽  
pp. 625-629 ◽  
Author(s):  
J P Revelli ◽  
R Pescini ◽  
P Muzzin ◽  
J Seydoux ◽  
M G Fitzgerald ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adrenergic Receptor ◽  
State Level ◽  
Total Density ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Displacement Experiments ◽  
Beta 2

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.

scholarly journals Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Van Schaik ◽  
C. Kettle ◽  
R. Green ◽  
W. Sievers ◽  
M. W. Hale ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Basolateral Amygdala ◽  
Free Breathing ◽  
Male Rats ◽  
Central Administration ◽  
Hypothalamic Area ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

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.

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