Effects of Initial Selenium Status on Apparent Dietary Selenium Requirements in Rodents

Robust biomarkers – that are specific for the nutrient, fall dramatically in deficiency, and reach well‐defined plateaus – are essential for the careful determination of dietary nutrient requirements (Adv Nutr 2016;7:1129). A second key component of dietary nutrient requirement studies is initial status at the start of an experiment. Se‐adequate male weanling rats fed Se‐deficient diets supplemented with graded levels of Se (as selenite) for 4 wk result in sigmoidal Se response curves with well‐defined plateaus for glutathione peroxidase (Gpx) activity, and with plateau breakpoints indicating minimum Se requirements of 0.06, 0.06, and 0.09 μg Se/g diet based on liver Gpx4, plasma Gpx3 and liver Gpx1 activity, respectively. Underlying these requirements, the Se requirement for liver Gpx1 mRNA is 0.06 μg Se/g diet. When second‐generation Se‐deficient weanling male rats were fed graded Se levels for 4 wk, apparent dietary Se requirements increased to 0.08, 0.1 and 0.14 μg Se/g for liver Gpx4, plasma Gpx3, and liver Gpx1 activities, respectively. The Se requirement for liver Gpx1 mRNA was 0.08 μg Se/g diet, which is 25% higher than when starting with Se‐adequate pups (Biol Trace Elem Res 2016, in press). Clearly, repleting Se‐deficient rats using an identical paradigm increased apparent dietary Se requirements by 33–67%, showing that limited dietary Se was being diverted to replete deeper body pools of Se. The higher dietary Se required to protect liver Gpx1 mRNA from nonsense mediated decay further substantiates this shift of Se from liver to other tissues. To explore in a preliminary study the role of Gpx1 mRNA and selenoprotein expression on restoration of Se status, Gpx1 wildtype ( Gpx1 +/+), heterozygote ( Gpx1 +/−), and knockout ( Gpx1 −/−) mice were fed Se‐deficient diets for 16 wk, then re‐supplemented with graded levels of dietary Se (0–0.3 μg Se/g) for 7 days to partially replete Gpx activities. Liver Gpx1 activity in Gpx1 +/+ mice reached a plateau with 0.15 μg Se/g, whereas in Gpx1 +/− mice, liver Gpx1 activity increased linearly over the full dietary range from 0 to 0.3 μg Se/g, showing the effect of limited Gpx1 mRNA as well as Se availability; there was no increase in Gpx1 activity in Gpx1 −/− mice, as expected. In contrast, red blood cell (RBC) Gpx1 activity was little altered by 0 to 0.15 μg Se/g in both Gpx1 +/+ and Gpx1 +/− mice, but then reached a similar level for both genotypes at 0.3 μg Se/g, suggesting that Se availability but not mRNA was controlling level of RBC Gpx1. The plasma Gpx3 activity Se response curve for Gpx1 +/+ mice was similar to the Se response curve for RBC Gpx1 activity for Gpx1 +/+ mice, only reaching a maximum at 0.3 μg Se/g. Surprisingly, the Se response curve for plasma Gpx3 activity in Gpx1 −/− mice overlay the response curve for Gpx1 +/+ mice, indicating that similar quantities of Se were transported to kidney for Gpx3 synthesis, whereas Gpx1 +/− mice fed 0.3 μg Se/g had considerable less Gpx3 activity than Gpx1 +/+ or Gpx1 −/− mice, again suggesting that Se was diverted to other tissues. Collectively, these studies illustrate that diversion of nutrient to depleted stores can result in higher apparent nutrient requirements when starting with initially depleted animals. Support or Funding Information Wisconsin Alumni Foundation Selenium Nutrition Research Fund (No. 2046295)