Lower Plasma Selenoprotein P Levels in Regularly Exercising Young Adults.

Objective: Physical exercise can provide many health benefits in humans. Exercise-induced reactive oxygen species (ROS) formation and its downstream signaling cascades are reported to induce mitochondrial biogenesis in exercising tissues. Selenoprotein P (SELENOP) is the antioxidant hepatokine whose hypersecretion is associated with various metabolic diseases. It was reported to impair exercise-induced reactive oxygen species signaling and inhibit subsequent mitochondrial biogenesis in mice. However, the relationship between selenoprotein P and mitochondrial dynamics in humans has not yet been reported. While reduction of plasma selenoprotein P becomes an attractive therapeutic target for metabolic diseases, the role of regular exercise in this regard is still unknown. This study aimed to analyze the influence of regular habitual exercise on plasma selenoprotein P levels and its association with leucocyte mitochondrial DNA copy number in healthy young adults. Methodology: Plasma selenoprotein P levels and leucocyte mitochondrial DNA copy numbers were compared in 44 regularly exercising subjects and 44 non-exercising controls, and the correlation between the two parameters was analyzed. Plasma selenoprotein P levels were measured by Enzyme-linked Immunosorbent Assay, and leucocyte mitochondrial DNA copy numbers were measured using the qPCR method. Results: The regular-exercise group had lower plasma selenoprotein P levels with higher leucocyte mitochondrial DNA copy numbers than the non-exercise group. There was a tendency of negative correlation between the two variables in our studied population. Conclusion: Regular habitual exercise has a beneficial effect on reducing plasma selenoprotein P levels while raising mitochondrial DNA copy numbers.

Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat.

Reactive oxygen species (ROS) activate uncoupler protein 1 (UCP1) in brown adipose tissue (BAT) under physiological cold exposure and noradrenaline (NA) stimulation to increase thermogenesis. However, the endogenous regulator of ROS in activated BAT and its role in pathological conditions remain unclear. We show that serum levels of selenoprotein P (SeP; encoded by SELENOP) negatively correlate with BAT activity in humans. Physiological cold exposure downregulates Selenop in BAT. Selenop knockout mice show higher rectal temperatures and UCP1 sulfenylation during cold exposure. SeP treatment to brown adipocytes eliminated the NA-induced mitochondrial ROS by upregulating glutathione peroxidase 4 and impaired cellular thermogenesis. A high-fat/high-sucrose diet elevates serum SeP levels and diminishes the elevated NA-induced thermogenesis in BAT-Selenop KO mice. Therefore, SeP is the intrinsic factor inducing reductive stress that impairs thermogenesis in BAT and may be a potential therapeutic target for obesity and diabetes.

Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.

We aimed to test the hypothesis that selenoprotein P (SELENOP), a hepatokine involved in the development of both insulin resistance and impaired insulin production in mice, is related to future onset of hyperglycemia in humans. 76 healthy non-pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-up. Nine subjects developed either impaired glucose tolerance or type 2 diabetes at follow-up. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP predicted fasting plasma glucose at follow-up independently of the other parameters. The receiver operating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was positively and independently associated with future onset of glucose intolerance in a general Japanese population.