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

Abstract

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 (T 4 ) or tri-iodothyronine (T 3 ) for five days and then exposed to cold (4 C, 24 h) or housed at room temperature (22 C). Under basal conditions, T 3 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 T 4 treatment. In T 3 -treated animals acutely exposed to cold stress, MDA concentration, an indicator of lipid peroxidation, was significantly higher compared with that of T 3 -treated animals housed at room temperature. However, in T 4 -treated animals, MDA concentrations were markedly lower. These results show that T 4 and T 3 differently affect IBAT parameters studied not only under basal but also under cold-stimulated conditions.

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…Decreases in CAT activities were found in brown adipose tissue after T3 or T4 treatment [130] and in liver [11,16], whereas lack of change [120,156,179] and decrease [11] were found in heart.…”

“…Although this may be true, it is interesting that in both mouse and rat hyperthyroidism was induced by T4, whose biological activity can differ from T3 in some tissues. Indeed, recent studies have shown that T4, but not T3, increases lipid peroxidation in rat interscapular brown adipose tissue [130].…”

Oxidative stress in cold-induced hyperthyroid state

“…Mitochondria should be the principal source of O 2 radicals in activated BAT, whereas smaller amounts would arise from peroxisomes (Cannon et al, 1982) and microsomes (Ramasarma, 1982;Sekhar et al, 1990). Increased activity of the H 2 O 2 -producing enzyme monoamino oxidase (MAO) was also found in coldexposed rats (Petrovic et al, 2003).…”

“…Information on thyroid hormone effects on oxidative damage of interscapular BAT are scant since only a recent study has shown that 5days of T 4 administration (300mgkg -1 body mass) to euthyroid rats, but not of T 3 , increased lipid peroxidation in rat BAT (Petrovic et al, 2003).…”

“…The high increase in H 2 O 2 production by the BAT mitochondrial respiratory chain induced by cold is surprising enough considering that cold-induced thermogenesis in BAT is associated with upregulation of uncoupling protein-1 (UCP1) (Petrovic et al, 2003) and uncoupling protein-3 (UCP3) (Larkin et al, 1997), two members of a subfamily of mitochondrial carriers, which are expressed in BAT and seem to be able to control ROS production. This is demonstrated by the observation that UCP1 inhibition actives H 2 O 2 generation in brown fat mitochondria (Nègre-Salvayre et al, 1997) and ROS production in UCP3 knockout mice is higher than that in wild-type mice (Vidal-Puig et al, 2000).…”