Dual-specificity phosphatase (Dusp8) has previously been identified as type 2 diabetes risk gene in humans that is highly expressed in the brain. Dusp8 acts as physiological inhibitor for mitogen-activated protein (MAP) kinases, which are involved in multiple CNS processes. Recently, we reported that hypothalamic Dusp8 acts as rheostat for Janus Kinase (Jnk) 1 in the arcuate nucleus and as critical gatekeeper for hypothalamus pituitary adrenals (HPA) axis functionality, hypothalamic insulin resistance and systemic glucose tolerance. In our follow-up studies, we aimed to dissect whether aberrant CNS insulin sensitivity and HPA axis control in our Dusp8 KO model are also interlinked with behavioral alterations. Among other behavioral test, we subjected Dusp8WT and KO mouse littermates to Resident Intruder tests and found a marked increase in intermale aggression in the Dusp8 KO mice. Stainings of WT and Dusp8 KO brains for cFOS, a marker for neuronal activity, revealed significant changes in two distinct areas known to gate aggressive behavior, the lateral septum (LS) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). Laser capture microdissection and RNASeq in these brain regions identified differentially expressed genes that are currently being assessed for their roles as potential interaction partners in Dusp8-mediated male aggression control. In sum, in this ongoing study we aim to delineate whether a known risk gene for diabetes type 2, is also involved in aggression control.