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bioRxiv · 10.1101/353052

β-Blocker inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.

Seara, F. A. C.·Araujo, I. G.·Imperio, G. E.·Marassi, M. P.·Silva, A. C. M.·Mecawi, A. S.·Reis, L. C.·Olivares, E. L.
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Abstract

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for {beta}-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmoles T4/min.mg ptn) was dramatically increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (propranolol given in the drinking water, 0.5 g/L) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in MI group compared to MI-non treated one by 40 and 57 % 1 and 12 weeks after treatment respectively (P<0.05). Our data suggest that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintains low T3 state and improves cardiac function additionally.

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Seara, F. A. C., Araujo, I. G., Imperio, G. E., Marassi, M. P., Silva, A. C. M., Mecawi, A. S., Reis, L. C., Olivares, E. L.. 2018-06-21. β-Blocker inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.. https://doi.org/10.1101/353052

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