BACKGROUND

The amino acid selenocysteine (Sec) is an integral part of selenoproteins, a class of proteins mostly involved in strong redox reactions. The enzyme Sec lyase (SCLY) decomposes Sec into selenide allowing for the recycling of the selenium (Se) atom via the selenoprotein synthesis machinery. We previously demonstrated that disruption of the Scly gene (Scly KO) in mice leads to the development of obesity and metabolic syndrome, with effects on glucose homeostasis, worsened by Se deficiency or a high-fat diet, and exacerbated in male mice. Our objective was to determine whether Se supplementation could ameliorate obesity and restore glucose homeostasis in the Scly KO mice.

METHODS

Three-weeks old male and female Scly KO mice were fed in separate experiments a diet containing 45 % kcal fat and either sodium selenite or a mixture of sodium selenite and selenomethionine (selenite/SeMet) at moderate (0.25 ppm) or high (0.5–1 ppm) levels for 9 weeks, and assessed for metabolic parameters, oxidative stress and expression of selenoproteins.

RESULTS

Se supplementation was unable to prevent obesity and elevated epididymal white adipose tissue weights in male Scly KO mice. Serum glutathione peroxidase activity in Scly KO mice was unchanged regardless of sex or dietary Se intake; however, supplementation with a mixture of selenite/SeMet improved oxidative stress biomarkers in the male Scly KO mice.

CONCLUSION

These results unveil sex- and selenocompound-specific regulation of energy metabolism after the loss of Scly, pointing to a role of this enzyme in the control of whole-body energy metabolism regardless of Se levels.

中文翻译：

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硒补充剂对硒代半胱氨酸裂解酶基因破坏小鼠饮食诱导肥胖的影响。

背景

氨基酸硒代半胱氨酸 (Sec) 是硒蛋白的组成部分，硒蛋白是一类主要参与强氧化还原反应的蛋白质。Sec 裂解酶 (SCLY) 将 Sec 分解为硒化物，允许通过硒蛋白合成机制回收硒 (Se) 原子。我们之前已经证明，小鼠Scly基因 (Scly KO) 的破坏会导致肥胖和代谢综合征的发展，影响葡萄糖稳态，因缺硒或高脂肪饮食而恶化，并在雄性小鼠中加剧。我们的目标是确定硒补充剂是否可以改善 Scly KO 小鼠的肥胖和恢复葡萄糖稳态。

方法

三周大的雄性和雌性 Scly KO 小鼠在单独的实验中被喂食含有 45% 千卡脂肪和亚硒酸钠或亚硒酸钠和硒代甲硫氨酸的混合物（亚硒酸盐/SeMet）的中等（0.25 ppm）或高（0.5– 1 ppm) 水平 9 周，并评估代谢参数、氧化应激和硒蛋白的表达。

结果

在雄性 Scly KO 小鼠中，硒补充剂无法预防肥胖和附睾白色脂肪组织重量升高。无论性别或膳食硒摄入量如何，Scly KO 小鼠的血清谷胱甘肽过氧化物酶活性都没有变化；然而，补充亚硒酸盐/SeMet 的混合物可以改善雄性 Scly KO 小鼠的氧化应激生物标志物。

结论

这些结果揭示了失去 Scly 后能量代谢的性别和硒化合物特异性调节，指出这种酶在控制全身能量代谢中的作用，而不管硒水平如何。