Metabolic dysfunctions following chronic oral corticosterone are modified by adolescence and sex in mice.

Adolescence is a period of development in which shifts in responses to glucocorticoids is well-documented. Obesity and metabolic syndrome are substantial health issues whose rates continue to rise in both adult and adolescent populations. Though many interacting factors contribute to these dysfunctions, how these shifts in glucocorticoid responses may be related remain unknown. Using a model of oral corticosterone (CORT) exposure in male and female mice, we demonstrate differential responses during adolescence (30-58 days of age) or adulthood (70-98 day of age) in endpoints relevant to metabolic function. Our data indicate that CORT resulted in significant weight gain in adult- and adolescent-exposed females and adult-exposed males, but not adolescent-exposed males. Despite this difference, all animals treated with high levels of CORT showed significant increases in white adipose tissue, indicating a dissociation between weight gain and adiposity in adolescent-treated males. Similarly, all experimental groups showed significant increases in plasma insulin, leptin, and triglyceride levels, further suggesting potential disconnects between overt weight gain, and underlying metabolic dysregulation. Finally, we found age- and dose-dependent changes in the expression of hepatic genes important in glucocorticoid receptor and lipid regulation, which showed different patterns in males and females. Thus, altered transcriptional pathways in the liver might be contributing differentially to the similar metabolic phenotype observed among these experimental groups. We also show that despite little CORT-induced changes in the hypothalamic levels of orexin-A and NPY, we found that food and fluid intake were elevated in adolescent-treated males and females. These data indicate chronic exposure to elevated glucocorticoid levels results in metabolic dysfunction in both males and females, which can be further modulated by developmental stage.