Hyperlipidemia (i.e. high levels of extracellular lipids) and obesity (i.e. high levels of intracellular lipids) can increase GSK3 activity via (i) suppression/overstimulation of the PI3K/Akt pathway and (ii) dissociation of GSK3/PLIN2. This evidence concerns the gene PLIN2 and obesity due to melanocortin 4 receptor deficiency.