Objective: This study aims to identify whether the development of insulin resistance (IR) induced by high selenium (Se) is related to serine deficiency via the inhibition of the de novo serine synthesis pathway (SSP) by the administrations of 3-phosphoglycerate dehydrogenase (PHGDH) inhibitor (NCT503) or exogenous serine in mice. Here, PHGDH is linked to neurometabolic disorder due to serine deficiency.