A novel selenoglycoside compound GlcSeCys alleviates diets-induced obesity and metabolic dysfunctions with the modulation of Galectin-1 and selenoproteins.

Abstract

Selenium, an essential trace element in human, has been shown to play protective roles in obesity and metabolic disorders despite insufficient understanding of mechanisms. Moreover, it's well known that biological actions of selenium compounds differed greatly due to divergent chemical forms. Selenoglycoside is a type of organoselenium compounds with excellent hydrophilicity, but biological activity of which in vivo are almost unknown. We have designed and synthesized Se-β-d-glucopyranosyl-D-selenocysteine, a novel selenoglycoside compound named GlcSeCys. Herein, GlcSeCys was given to high fat high cholesterol (HFHC) fed mice to determine its actions as well as relevant molecular mechanisms using transcriptome and multiple molecular biological methods. It was revealed that GlcSeCys displayed pronounced anti-obesity effect and significantly alleviated hyperglycemia, hyperinsulinemia along with hepatic steatosis in HFHC diets-induced mice. Mechanistically, GlcSeCys was found to inhibit lipogenesis, lipid uptake and inflammation in liver, along with attenuation of Galectin-1 and induction of selenoprotein S (SELENOS). With regard to adipose tissues, GlcSeCys ameliorated hypertrophy of adipocytes, suppressed lipids biosynthesis and stimulated WAT browning along with abrogated WAT inflammation activation, which were in line with repression of Galectin-1 and increase of GPx3. Collectively, our results uncovered, for the first time, that selenoglycoside compound GlcSeCys possessed excellent protective effects against obesity and metabolic disorders, and the mechanisms were correlated with modulation of Galectin-1 and selenoproteins, shedding lights upon molecular biology of selenium and novel therapeutic for obesity and relevant metabolic disorders.