PIK3C3 and fatty liver disease: Consistently, in response to high-fat diet treatment, partial suppression of the VPS34 kinase by systemic heterozygous expression of a kinase-dead VPS34 mutant (Vps34D761A/+), as well as VPS34 inhibitor treatment, suppresses hepatic steatosis and enhances glucose tolerance and insulin sensitivity, via suppression of metabolic substrate supplies to mitochondria, activation of AMPK signaling pathway, and increase of fatty acid β-oxidation (Bilanges et al., 2017).