Type 2 diabetes (T2D) and Alzheimer’s disease (AD) share several common pathophysiological features.Huperzine A (Hup A),a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata,is a specific and reversible inhibitor of acetylcholinesterase,which is clinically used for the treatment of AD.In this study,we investigated whether Hup A improved the metabolic and cognitive functions in the high fat-induced (HFD) obese mice and genetic ob/ob mice.HFD and ob/ob mice were treated with Hup A (0.1,0.3 mg· kg-1· d-1,ig) for 3 months.Body weight was monitored and glucose tolerance tests were performed.Novel object recognition test and Morris water maze assay were conducted to evaluate the cognitive functions.We found that the Hup A treatment had no significant effect on peripheral metabolism of obese mice,whereas Hup A (0.1,mg· kg-1· d-1) improved both the abilities of object recognition and spatial memory in HFD-fed mice,but not in ob/ob mice.Furthermore,Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice,but not ob/ob mice.In addition,Hup A (0.3,mg· kg-1· d-1) significantly decreased cortical β-secretase (BACE1) expression.In conclusion,these results demonstrate that treatment with Hup A (0.1,mg· kg-1· d-1) can effectively improve the cognitive functions,at least in diet-induced obese mice.