Selenium Deficiency during Pregnancy in Mice Impairs Exercise Performance and Metabolic Function in Adult Offspring

Abstract

Selenium deficiency during the perinatal period programs metabolic dysfunction in offspring. Postnatal exercise may prevent the development of programmed metabolic disease. This study investigated the impact of selenium deficiency on offspring exercise behavior and whether this improved metabolic health. Female C57BL/6 mice were randomly allocated to control (NormalSe, >190 μg/Se/kg, n = 8) or low-selenium (LowSe, <50 μg/Se/kg, n = 8) diets from four weeks before mating. Male offspring were weaned at postnatal day (PN) twenty-four and placed on a normal chow diet. At PN60, mice were placed in cages with bi-directional running wheels and monitored until PN180. LowSe offspring had a reduced average weekly running speed and distance (p < 0.05). LowSe offspring exhibited glucose intolerance, with increased peak blood glucose (p < 0.05) and area under the curve following an intra-peritoneal injection of glucose (p < 0.05). Furthermore, mRNA expression of several selenoproteins within cardiac and skeletal muscle were increased in LowSe offspring (p < 0.05). The results indicated that selenium deficiency during development reduces exercise behavior. Furthermore, exercise does not prevent programmed glucose intolerance in low-selenium offspring. This highlights that exercise may not be the optimal intervention for metabolic disease in offspring impacted by selenium deficiency in early life.

Keywords: DOHaD; metabolism; physical activity; selenoproteins.

Figure 1

Exercising mice body weight, food and water consumption. Exercising male mice (A) body weight at PN180 as well as average (B) food and (C) water consumption from weaning to PN180. Data are mean ± SEM and analyzed by unpaired t-test. Significance determined by p < 0.05. n = 6.

Figure 2

Exercise behavior from PN60 to PN180. Exercise behavior in male mice from normal and low-selenium litters. (A) Cumulative running distance from PN60 to PN180. (B) Average weekly running distance, (C) speed and (D) time over four months. Cumulative data are mean ± SEM and analyzed by two-way ANOVA with treatment (Ptrt) and time (Ptime) as major factors. Pint represents the interaction between Ptrt and Ptime. Multiple comparisons were determined by Sidak post hoc testing. Distance, speed and time data were analyzed by unpaired t-test. * = p < 0.05, ** = p < 0.01 compared to the control exercise group. n= 6.

Figure 3

Glucose tolerance and resting blood glucose analysis. PN170 glucose tolerance testing showing (A) GTT AUC as well as (B) peak blood glucose 30 min post-IP and (C) 180 min post-IP. (D) PN90 and (E) PN180 fasting blood glucose levels. Data are mean ± SEM and analyzed by unpaired t-test. * = p < 0.05. n = 6 per group.