Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors

Abstract

The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.

Dietary selenate attenuates adiposity and improves insulin sensitivity in high-fat diet-induced obese mice

“…Although selenoproteins largely act as redox regulators for cellular anti-oxidant homeostasis, some selenoproteins, such as glutathione peroxidase 1 (GPx1) (McClung et al, 2004), selenoprotein P (Choi et al, 2013;Ko, Kim, Park, Park, & Mantzoros, 2014;Zhang & Chen, 2011), selenoprotein M (Pitts et al, 2013), and selenoprotein S Olsson et al, 2011), and selenocysteine lyase (Seale et al, 2012), were reported to be associated with modulation of adiposity and its related metabolic disorders. Interestingly, we recently demonstrated an inhibitory role of selenoprotein S in the ubiquitin-proteasome system in adipocytes and during adipogenesis .…”

Diet-Induced Obesity in the Selenocysteine Lyase Knockout Mouse

“…WAT after treatment with insulin (45). In our model, the animals are severely hyperinsulinemic, however, it is unknown whether their WAT depots are insulin resistant as well.…”

Selenium biochemistry and its role for human health

“…222 In vitro studies demonstrated also that SelP expression in human subcutaneous adipocytes is up-regulated by insulin. 223 TrxRs may positively influence insulin signalling by providing reducing equivalents in the form of Trx. In skeletal muscle, proteins S-nitrosylation operated by NO has been proposed to contribute to the induction of muscle insulin resistance.…”