Laureano-Melo Roberto, Império Güínever E, Kluck George E G, da Conceição Rodrigo R, de Souza Janaina S, Marinho Bruno G, Giannocco Gisele, Côrtes Wellington S
Department of Physiological Sciences, Multicenter Graduate Program in Physiological Sciences, Institute of Health and Biological Sciences, Federal Rural University of Rio de Janeiro, Seropedica, Brazil.
Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Rio de Janeiro, Brazil.
Clin Exp Pharmacol Physiol. 2020 Jul;47(7):1272-1282. doi: 10.1111/1440-1681.13268. Epub 2020 Mar 22.
Epidemiological and animal studies have demonstrated a strong association between selenium (Se) supplementation and metabolic disorders, we aimed to evaluate whether maternal Se supplementation was able to change metabolic parameters in rats' offspring. Moreover, as Se is a deiodinase (DIO) cofactor, we decided to investigate how thyroid hormones (THs) would be involved in such metabolic changes. Thereby, two groups (n = 6, ~250 g) of female Wistar rats underwent isotonic saline or sodium selenite (1 mg/kg, p.o.) treatments. Although there were no significant differences in body weight between groups, the Se treatment during pregnancy and lactation increased milk intake and the visceral white adipose tissue (WAT) in offspring. The rats whose mothers were treated with Se also presented an improvement in the glucose tolerance test and in the glucose-stimulated insulin secretion. Regarding the lipid metabolism, the Se group had a reduction of triglycerides in the liver and in WAT. These metabolic changes were accompanied by an increase in serum triiodothyronine (T ) and in DIO 2 expression in brown adipose tissue (BAT). We further demonstrate an increased expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1) mRNA in the liver. In adulthood offspring, Se supplementation programs thyroid function, glucose homeostasis, and feeding behaviour. Taken together, there is no indication that Se programming causes insulin resistance. Moreover, we conjecture that these metabolic responses are induced by increased thyroxine (T ) to T conversion by DIO2 in BAT and mediated by altered transcription factors expression associated with oxidative metabolism control in the liver.
流行病学和动物研究表明，补充硒（Se）与代谢紊乱之间存在密切关联。我们旨在评估母体补充硒是否能够改变大鼠后代的代谢参数。此外，由于硒是脱碘酶（DIO）的辅因子，我们决定研究甲状腺激素（THs）如何参与这种代谢变化。因此，两组（n = 6，约250 g）雌性Wistar大鼠分别接受等渗盐水或亚硒酸钠（1 mg/kg，口服）治疗。尽管两组之间体重没有显著差异，但孕期和哺乳期的硒治疗增加了后代的牛奶摄入量和内脏白色脂肪组织（WAT）。母亲接受硒治疗的大鼠在葡萄糖耐量试验和葡萄糖刺激的胰岛素分泌方面也有所改善。在脂质代谢方面，硒组肝脏和WAT中的甘油三酯减少。这些代谢变化伴随着血清三碘甲状腺原氨酸（T）的增加以及棕色脂肪组织（BAT）中DIO 2表达的增加。我们进一步证明肝脏中过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）和核呼吸因子-1（NRF-1）mRNA的表达增加。在成年后代中，补充硒可调节甲状腺功能、葡萄糖稳态和摄食行为。综上所述，没有迹象表明硒编程会导致胰岛素抵抗。此外，我们推测这些代谢反应是由BAT中DIO2将甲状腺素（T）转化为T增加所诱导，并由肝脏中与氧化代谢控制相关的转录因子表达改变介导。
