జర్నల్ ఆఫ్ క్లినికల్ టాక్సికాలజీ
అందరికి ప్రవేశం
ISSN: 2161-0495
ISSN: 2161-0495
Yifan Lv, Shouqing Liu, Jia Tong, Qianqian Zhang, Zhongjian Zhang, Shiyong Peng, Shihong Li, Ni Yang,Weiyong Li, Wenqiang Li
Olanzapine, a widely used antipsychotic, causes significant iatrogenic side effects of obese leading to non-compliance of antipsychotics in schizophrenia patients. However, the mechanism of olanzapine creating obese of metabolic disorders has remained elusive till now. Adipocyte proliferation was believed as general reasons for obesity-related diseases, convinced from our olanzapine-induced obese rat model. Our results demonstrated adipocyte proliferation through significantly elevating P-PI3K and P-AKT cascades in chronic treatment of olanzapine. Interestingly, significant activations of apoptosis through Klotho-Egr-1-MnSOD pathway were also observed in the obese rat model. We hypothesized that the activation of the apoptotic pathway could elicit a feedback response in adipocyte proliferation after olanzapine chronic treatments. Our results demonstrated that olanzapine-induced apoptosis responses on 3T3-L1 adipocytes in a dose-dependent manner, while significant adipocyte proliferation was only visible in a range of 5 μM olanzapine which is a general dose concentration in clinic applications. Furthermore, administrations of recombinant Klotho peptide could restrict the activation of apoptosis by olanzapine in clinic dosage and then inhibited feedback response of adipocyte proliferation. The current study shed lights on appeasing olanzapine-induced obese syndromes through a new target of blocking apoptotic activation by recombinant klotho and then improving the therapeutic effect of olanzapine.