Moreover, to deeply investigate the critical role of zDHHC3-mediated hyper-palmitoylation in HFD-dependent cognitive impairment, we specifically inhibited the expression of palmitoyltransferase in mice fed with SD or HFD by intrahippocampal injection of lentivirus harboring shRNA against zDHHC3 (LV-shzDHHC3) (Supplementary Fig. 4a). Here, ZDHHC3 is linked to Cognitive impairment.