ArticleScientific reports2022
Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- 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
- Article
- A pumpless liver-adipose model for studying metabolic dysfunction and drug responses.PloS one · 2026Article
- GLUT5-Driven Gut-Liver Axis Injury Mediating Olanzapine-Induced NAFLD and Dapagliflozin Intervention.Drug design, development and therapy · 2026Article
- Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options.Lipids in health and disease · 2025Review
- Article
- Tunable Intranasal Polymersome Nanocarriers Triggered Olanzapine Brain Delivery and Improved In Vivo Antipsychotic Activity.Pharmaceutics · 2025Article
- Olanzapine-induced metabolic syndrome is partially mediated by oxytocinergic system dysfunction in female Sprague-Dawley rats.PloS one · 2025Article
- Olanzapine and peripheral metabolic dysregulation: organ-resolved mechanisms, risk, and MASLD-aligned care pathways.Frontiers in pharmacology · 2025Review
- Article
- 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
- The regulatory effects of second-generation antipsychotics on lipid metabolism: Potential mechanisms mediated by the gut microbiota and therapeutic implications.Frontiers in pharmacology · 2023Review
- Vitamin D supplementation is effective for olanzapine-induced dyslipidemia.Frontiers in pharmacology · 2023Article
- Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid β-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.
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