Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

Abstract

Selenoprotein F (SELENOF) might play an important role in maintaining human health since an increasing number of studies have linked SELENOF deficiency to various pathologies such as cancer and neurodegeneration. We have previously reported on glucose metabolism disorders in SELENOF knockout mice, which imply a novel biological function of SELENOF in glucose metabolism. However, the underlying mechanism and whether the effect of SELENOF on glucose metabolism is age-dependent remain unknown. In the present study, we compare the metabolic phenotype in more detail as well as the oxidative stress parameters in SELENOF knockout mice (C57BL/6J background) and naïve C57BL/6J mice of different ages (12, 16 and 21 weeks old). The results showed that SELENOF knockout caused glucose metabolism disorders only in young mice, especially in 12-week-old mice, characterized by hyperglycemia, serum insulin reduction, impaired glucose tolerance, decreased insulin sensitivity, decreased glucose catabolism, increased gluconeogenesis and impaired insulin signaling pathway. These abnormalities gradually improved with age and disappeared in knockout mice at 21 weeks old. Furthermore, before 16 weeks old, SELENOF knockout mice showed increased lipid peroxidation and decreased glutathione/glutathione disulfide ratio and glutathione peroxidase activity in the serum and liver. Furthermore, the expression of glutathione peroxidase 1 significantly reduced in the liver and pancreas. Our findings suggest that SELENOF knockout might cause glucose metabolism disorders in young mice via the disruption of redox homeostasis.

Distinct Roles of SELENOF in Different Human Cancers

“…Overall, these data indicate that the loss of Selenof exacerbates the metabolic syndrome when animals are exposed to a high fat diet. In contrast, a more recent examination showed that glucose metabolism differences are significant in younger SELENOF KO mice (12 weeks old) via the disruption of redox homeostasis; however, these differences tended to dissipate with age (16 weeks and older) [ 54 ]. Metabolic dysregulation also occurs when diets with excess selenium are consumed by mice and rats [ 55 , 56 ].…”

SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells

“…Given SELENOF's cellular localization within the EnR and its redox activity, it is postulated to play a putative role in disulfide-bond formation and protein redox quality control [10,11]. More recently, depletion of SELENOF in cultured human cells or in Selenof knockout animal models was shown to result in differential expression of metabolism-related genes and associated phenotypes [12][13][14][15][16][17]. In this study, SELENOF-driven functions and phenotypes were examined in normal breast epithelial and breast cancer cells to better understand the role of SELENOF in breast cancer and to identify potential new therapeutic strategies.…”