A role for AMP-activated protein kinase in the mediation of metabolic disturbances induced by olanzapine

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Olanzapine (OLA) is known to be advantageous with respect to outcome and drug compliance in patients with schizophrenia. However, OLA has unwanted effects, including a higher incidence of weight gain and metabolic disturbances. In this study, we demonstrated that (1) neuropeptides-mediated activation of hypothalamic AMPK and subsequent enhancement of orexigenic signal may mediate hyperphagia and weight gain induced by chronic treatment with OLA, (2) OLA enhanced glycogenolysis in hepatocyte contributes to the development of hyperglycemia, (3) AMPK-SREBP pathway is responsible for OLA-induced hyperlipidemia.