Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs

While selenium (Se) is an essential micronutrient for humans, epidemiological studies have raised concern that supranutritional Se intake may increase the risk of developing Type 2 diabetes mellitus (T2DM). We aimed to determine the impact of Se at a dose and source frequently ingested by humans on markers of insulin sensitivity and signalling. Male pigs were fed either a Se-adequate (0.17 mg Se/kg) or a Se-supranutritional (0.50 mg Se/kg; high-Se) diet. After 16 weeks of intervention, fasting plasma insulin and cholesterol levels were non-significantly increased in the high-Se pigs, whereas fasting glucose concentrations did not differ between the two groups. In skeletal muscle of high-Se pigs, glutathione peroxidase activity was increased, gene expression of forkhead box O1 transcription factor and peroxisomal proliferator-activated receptor-γ coactivator 1α were increased and gene expression of the glycolytic enzyme pyruvate kinase was decreased. In visceral adipose tissue of high-Se pigs, mRNA levels of sterol regulatory element-binding transcription factor 1 were increased, and the phosphorylation of Akt, AMP-activated kinase and mitogen-activated protein kinases was affected. In conclusion, dietary Se oversupply may affect expression and activity of proteins involved in energy metabolism in major insulin target tissues, though this is probably not sufficient to induce diabetes.

Graphical abstractInfluence of a supranutritional selenium diet on the insulin-regulated energy metabolism in pigs. Selenium may induce metabolic and molecular alterations, resulting in an increase in lipid turnover and a shift in fuel selection from carbohydrates to lipids in skeletal muscle and visceral adipose tissue.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights►Feeding pigs a 16-week supranutritional selenium diet resulted in hyperinsulinaemia. ► Supranutritional Se intake (0.5 mg Se/kg) was not sufficient to induce diabetes. ► Selenoprotein biosynthesis was largely saturated in adequate-Se (0.17 mg Se/kg) pigs. ► Molecular alterations in adipose tissue and skeletal muscle suggest increased lipid turnover.