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

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 β-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 the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly 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 (0.5 g/L propranolol given in the drinking water) 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 the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Brown adipose tissue: what have we learned since its recent identification in human adults / Tecido adiposo marrom: o que aprendemos desde sua recente identificação em humanos adultos

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

O tecido adiposo marrom, órgão essencial para a termorregulação de animais hibernantes e pequenos devido à sua capacidade desacopladora, era até poucos anos considerado presente apenas em recém-nascidos na espécie humana. A identificação do tecido adiposo marrom em adultos com o desenvolvimento e uso da tomografia de emissão de pósitron marcado com 18-fluorodesoxiglicose (PET-FDG) gerou questões sobre sua real importância para nosso metabolismo. Nesta revisão, discutiremos o que aprendemos nesse tempo, assim como conceitos antigos e novos, alguns marginalizados por décadas, como a termogênese induzida por dieta. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

El cinc inhibe la conversion de tiroxina en triidotironina en grasa parda in vitro / Zinc inhibits the in vitro conversion of thyroxine to triidothyronine in brown adipose tissue

Se estudió el efecto del cinc sobre la conversión de tiroxina (T4) a triodotironina (T3) en homogenatos de grasa parda de ratas expuestas a temperaturas de 4 grados Celsius o 22 grados Celsius durante 24 h. Luego de sacrificar a los animales por dislocación cervical, se extrajo la grasa parda interescapular y se homogeneizó en buffer sacarosa (320 mM) y HEPES (10 mH) pH 7.4. Se centrifugó el preparado a 4 grados Celsius y se separó la capa que contiene la actividad 5'-deiodinasa. Se separaron alícuotas a las que se agregaron 50, 100 muM, 1 o 5 mM sulfato de cinc, más 0.5, 10 o 25 mM ditiotreitol (DTT) y 1 muCi (125)I-T4. El preparo se incubó a 37 grados Celsius durante 60 min luego de lo cual se hizo cromatografía en papel para separar los diferentes compuestos radioactivos del homogenato. En ratas mantenidas a 22 grados Celsius, la deiodinación de T4 produjo 13.3 por ciento de T3, equivalente a 79 + 30 pg/mg proteina/h. Las dosis de 1 y 5 mM cinc inhibieron significativamente la producción de T3, En ratas expuestas a 4 grados Celsius, la producción basal de T3 se incrementó a 248 + 37 pg/mg proteina/h. Al agregar cinc en dosis de 100 muM, 1 o 5 mM, se redujo significativamente la deiodinación de T4. La acción inhibidora del sinc sobre la producción de T3 en la grasa parda tendría efectos deletéreos sobre la termogénesis en ese tejido.

Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 ñ 0.31 vs CL = 23.64 ñ 0.30 g/l, P<0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 ñ 26 vs CL = 535.41 ñ 54 mg, P<0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 ñ 3.2 vs CL = 227.14 ñ 1.7 mg/g, P<0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ñ 1.1 vs CL = -10.2 ñ 1.9 g, P<0.05). This was associated with a marked decrease in fat stores (P = 5.35 ñ 0.81 vs CL = 2.02 ñ 0.16 g, P<0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ñ 16.20 vs CL = 414.48 ñ 11.32 U/BAT x kg body weight, P<0.05), was still much higher than in control rats (C = 159.55 ñ 11.54 vs CL = 414.48 ñ 11.32 U/BAT x kg body weight, P<0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet