AUTHOR=Huang Piao-Piao , Zhu Wen-Qiang , Xiao Jing-Mei , Zhang Yi-Qi , Li Rong , Yang Yang , Shen Li , Luo Fei , Dai Wen , Lian Ping-An , Tang Ya-Xin , Ran Juan-Li , Huang Xian-Sheng TITLE=Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.935362 DOI=10.3389/fphar.2022.935362 ISSN=1663-9812 ABSTRACT=
Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic