Abstract
Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs' good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity.