Isabella Mezzani

Selenium (Se) is an essential micronutrient required for redox regulation and metabolic homeostasis. Altered biomarkers of Se status have been linked with obesity and metabolic syndrome, yet its role in these conditions, particularly in a sex-specific context, is not well defined. This study investigated the impact of suboptimal Se intake on metabolic risk profiles in male and female mice with pre-existing diet-induced obesity. C57BL/6N mice were fed either a standard diet with adequate Se (SD-ASe), a Western diet with adequate Se (WD-ASe), or WD-ASe followed by a Western diet containing suboptimal Se levels (WD-SOSe). Metabolic parameters, adipokine profiles, tissue Se distribution, and gene expression in visceral white adipose tissue (vWAT) were assessed. Both sexes exhibited increased weight gain and adiposity in response to a Western diet; however, only males developed hypertension and elevated non-fasted blood glucose levels. Suboptimal Se intake elicited marked sex-dependent effects. In females, it induced elevated non-fasted blood glucose levels and circulating leptin, and further dysregulated circulating adipokine profiles, accompanied by pronounced alterations in selenoprotein expression and redox-related pathways in vWAT. In contrast, male mice exhibited a partial adaptation, including reduced glucose levels and minimal alterations in gene expression. Tissue Se distribution also appeared to be influenced by biological sex. These findings demonstrate that suboptimal Se intake may exacerbate obesity-related metabolic dysfunction in a sex-specific manner, with females showing greater susceptibility, underscoring the importance of micronutrient status and sex differences in metabolic disorders.