Moreover, in mouse models systemic administration of irisin, which is able to cross the blood–brain barrier (Islam et al., 2021; Wrann et al., 2013), significantly increased the expression of the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha) and fibronectin type III domain-containing protein 5 (FNDC5), the precursor of irisin, in both the hippocampus and prefrontal cortex, two brain areas involved in depression (Dicarlo et al., 2023). The gene discussed is FNDC5; the disease is major depressive disorder.