scholarly journals Thyroxine and tri-iodothyronine differently affect uncoupling protein-1 content and antioxidant enzyme activities in rat interscapular brown adipose tissue

2003 ◽  
Vol 176 (1) ◽  
pp. 31-38 ◽  
Author(s):  
N Petrovic ◽  
G Cvijic ◽  
V Davidovic

The activity of the antioxidant enzymes copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity, uncoupling protein-1 (UCP1) content, catecholamine degrading enzyme monoamine oxidase (MAO) activity and malonyl dialdehyde (MDA) concentration were studied in rat interscapular brown adipose tIssue (IBAT). Rats were treated with either thyroxine (T4) or tri-iodothyronine (T3) for five days and then exposed to cold (4 degrees C, 24 h) or housed at room temperature (22 degrees C). Under basal conditions, T3 treatment significantly increased UCP1 content and MnSOD activity whereas CuZnSOD, CAT and MAO activities were significantly decreased. Thyroxine treatment significantly decreased IBAT CAT activity while MDA levels markedly increased. Cold exposure induced a significant augmentation of UCP1 content and MnSOD and mGPDH activities only in animals that were rendered hyperthyroid by T4 treatment. In T3-treated animals acutely exposed to cold stress, MDA concentration, an indicator of lipid peroxidation, was significantly higher compared with that of T3-treated animals housed at room temperature. However, in T4-treated animals, MDA concentrations were markedly lower. These results show that T4 and T3 differently affect IBAT parameters studied not only under basal but also under cold-stimulated conditions.

2008 ◽  
pp. 95-100
Author(s):  
A Perovic ◽  
T Vuckovic ◽  
G Cvijic ◽  
J Djordjevic ◽  
V Davidovic

The effect of exogenous noradrenaline (NA) (1.6 mg.kg-1 i.p., 35 min prior sacrifice) on the activity of antioxidant enzymes (AOE) copper zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as lipid peroxides (LP) concentration were studied in the rat interscapular brown adipose tissue (IBAT) and heart of saline (controls) and Nω-nitro-L-arginine methyl ester (L-NAME) treated rats (10 mg.kg-1, i.p., during 3 days and 20 min before NA). NA differently affects both AOE activities and LP production in the IBAT and heart. Thus, NA inhibited the activity of all IBAT AOE and LP production while in the heart it markedly increased CAT activity only, but had no effect on any of SODs activities and LP concentration. L-NAME, a nitric oxide synthase blocker, completely abolished the NA-induced inhibition of the IBAT AOE and LP production, whereas in the heart it was without effect. In conclusion, these results indicate that both NA and L-NAME effects on AOE activity and LP production are tissue specific and also suggest that nitric oxide mediates the NA-induced inhibition of AOE activity and LP production in the IBAT only.


1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.


2015 ◽  
Vol 112 (22) ◽  
pp. 6973-6978 ◽  
Author(s):  
Yang Lee ◽  
Chrissie Willers ◽  
Edmund R. S. Kunji ◽  
Paul G. Crichton

Uncoupling protein 1 (UCP1) catalyzes fatty acid-activated, purine nucleotide-sensitive proton leak across the mitochondrial inner membrane of brown adipose tissue to produce heat, and could help combat obesity and metabolic disease in humans. Studies over the last 30 years conclude that the protein is a dimer, binding one nucleotide molecule per two proteins, and unlike the related mitochondrial ADP/ATP carrier, does not bind cardiolipin. Here, we have developed novel methods to purify milligram amounts of UCP1 from native sources by using covalent chromatography that, unlike past methods, allows the protein to be prepared in defined conditions, free of excess detergent and lipid. Assessment of purified preparations by TLC reveal that UCP1 retains tightly bound cardiolipin, with a lipid phosphorus content equating to three molecules per protein, like the ADP/ATP carrier. Cardiolipin stabilizes UCP1, as demonstrated by reconstitution experiments and thermostability assays, indicating that the lipid has an integral role in the functioning of the protein, similar to other mitochondrial carriers. Furthermore, we find that UCP1 is not dimeric but monomeric, as indicated by size exclusion analysis, and has a ligand titration profile in isothermal calorimetric measurements that clearly shows that one nucleotide binds per monomer. These findings reveal the fundamental composition of UCP1, which is essential for understanding the mechanism of the protein. Our assessment of the properties of UCP1 indicate that it is not unique among mitochondrial carriers and so is likely to use a common exchange mechanism in its primary function in brown adipose tissue mitochondria.


2008 ◽  
Vol 19 (12) ◽  
pp. 840-847 ◽  
Author(s):  
Sachiko Nomura ◽  
Takashi Ichinose ◽  
Manabu Jinde ◽  
Yu Kawashima ◽  
Kaoru Tachiyashiki ◽  
...  

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