ArticlePsychopharmacology2022
PCSK9 mediates dyslipidemia induced by olanzapine treatment in schizophrenia patients.
Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Experimental pasta as an innovative approach to cholesterol reduction in patients with metabolic syndrome, with and without major psychiatric disorders: A randomized controlled trial supported byEuropean psychiatry : the journal of the Association of European Psychiatrists · 2025Trial
- PCSK9 at the intersection of lipid metabolism, immunometabolism, and psychiatric disorders: A narrative review.Brain, behavior, & immunity - health · 2026Review
- Real-World Evidence on Low-Dose Olanzapine (≤1.25 mg) for Personalized Antipsychotic Dosing.Journal of personalized medicine · 2025Article
- Atypical antipsychotic drugs cause abnormal glucose and lipid metabolism independent of weight gain.European archives of psychiatry and clinical neuroscience · 2025Article
- Uric acid and HDL-C-derived inflammatory ratios as biomarkers in schizophrenia and major depressive disorder: a retrospective study.Frontiers in psychiatry · 2025Article
- Olanzapine-induced metabolic syndrome is partially mediated by oxytocinergic system dysfunction in female Sprague-Dawley rats.PloS one · 2025Article
- Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers.Metabolites · 2024Review
- Research progress in the correlation between SREBP/PCSK9 pathway and lipid metabolism disorders induced by antipsychotics.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Review
- Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway.Scientific reports · 2022Article
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Authors and funding
16 authors.
Funding
Abstract
rationaleIt is controversial whether dyslipidemia induced by antipsychotics in schizophrenia patients is due to weight gain or direct effects of drug treatment. However, recent evidence showed that olanzapine can cause acute dyslipidemia independent of weight change, and the underlying mechanism remains unclear.
objectiveTo study the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in olanzapine-induced dyslipidemia, we analyzed in schizophrenic patients and in experimental models involving mice and cells to understand the mechanism.
methodsDisturbances in lipid homeostasis caused by 8-week olanzapine treatment were prospectively evaluated in first-episode schizophrenic patients. Additionally, mice were administered olanzapine for 5 or 8 weeks to delineate liver actions for PCSK9 contributing to olanzapine-induced dyslipidemia.
resultsOlanzapine directly affected lipid metabolism, suggesting dyslipidemia is independent of weight gain in schizophrenia patients. Olanzapine administration significantly increased plasma PCSK9, which was positively correlated with the increment in low-density lipoprotein cholesterol (LDL-C) (r=0.77, p<0.001). Increased expression of PCSK9 in liver tissue of olanzapine-treated mice occurred prior to olanzapine-induced LDL-C abnormality. Hepatic sterol regulatory element binding protein-2 (SREBP-2) protein levels increased in mice treated with olanzapine but largely declined in olanzapine (10μM) treated HepG2 cells, which suggested high concentration of olanzapine-induced PCSK9 increase was not SREBP-2-dependent. However, expressions of sterol regulatory element binding protein-1c (SREBP-1c) significantly increased in the higher dose treated groups, which was consistent with PCSK9 increases. Activation of SREBP-1c after high-dose olanzapine treatment promotes PSCK9 expression, and consequently the degradation of low-density lipoprotein receptors results in LDL-C increase.
conclusionsLipid disturbances caused by olanzapine are independent of weight gain. The study explored the relationship between SREBP-1c and PCSK9 in regulating lipoprotein metabolism after olanzapine treatment in vitro and in vivo. Further exploration of olanzapine-induced PCSK9 regulatory mechanisms may help identify control points for inhibition of olanzapine-mediated dyslipidemia.
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