HCRT and Insulin resistance: This dimorphism arises from opposing actions of gonadal steroids: testosterone enhances orexin neuron excitability and promotes insulin resistance upon orexin loss, whereas 17β-estradiol upregulates OX1R expression and potentiates insulin-sensitizing and β-cell-protective effects of orexin-A (Tsuneki et al., 2008; Hakizimana and Alagbonsi, 2025).