ArticleActa pharmacologica Sinica2019
Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Berberine and health outcomes: an overview of systematic reviews.BMC complementary medicine and therapies · 2025Pooled it
- Olanzapine-induced metabolic syndrome is partially mediated by oxytocinergic system dysfunction in female Sprague-Dawley rats.PloS one · 2025Article
- Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.Acta pharmacologica Sinica · 2024Article
- Modulation of Leucine Sensors to Mitigate Antipsychotics-Induced Metabolic Syndrome: A New Vista.ACS pharmacology & translational science · 2024Article
- Longitudinal Gut Microbiota Dysbiosis Underlies Olanzapine-Induced Weight Gain.Microbiology spectrum · 2023Article
- Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases.Inflammopharmacology · 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
- Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway.Scientific reports · 2022Article
- Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.Translational psychiatry · 2022Review
- Olanzapine-induced lipid disturbances: A potential mechanism through the gut microbiota-brain axis.Frontiers in pharmacology · 2022Article
- Possible Association of Cholesterol as a Biomarker in Suicide Behavior.Biomedicines · 2021Review
- A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.Psychopharmacology · 2021Article
- Brexpiprazole caused glycolipid metabolic disorder by inhibiting GLP1/GLP1R signaling in rats.Acta pharmacologica Sinica · 2021Article
- Beneficial effect ofJournal of diabetes and metabolic disorders · 2021Article
- Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Antidepressants- and antipsychotics-induced hepatotoxicity.Archives of toxicology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Second-generation antipsychotic drug (SGA)-induced metabolic abnormalities, such as dyslipidemia, are a major clinical problem for antipsychotic therapy. Accumulated evidences have shown the efficacy of statins in reducing SGA-induced dyslipidemia, but the underlying mechanisms are unclear. In this study, we explored whether mTOR signaling was involved in olanzapine (OLZ)-induced dyslipidemia as well as the lipid-lowering effects of cotreatment of simvastatin (Sim) in rats. Model rats received OLZ (1.0 mg/kg, t.i.d.) for 7 weeks; from the third week a group of model rats were cotreatment of Sim (3.0 mg/kg, t.i.d.) for 5 weeks. We found that OLZ treatment significantly increased the plasma triglyceride (TG) and total cholesterol (TC) levels, and promoted lipid accumulation in the liver, whereas cotreatment of Sim reversed OLZ-induced dyslipidemia. Hepatic mTORC1 and p-mTORC1 expression was accelerated in the OLZ treatment group, with upregulation of mRNA expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, whereas these alterations were ameliorated by Sim cotreatment. In HepG2 cells, rapamycin (a mTOR inhibitor) significantly reduced the OLZ-stimulated hepatocellular lipid contents and weakened the ability of Sim to lower lipids via a mechanism associated with the upregulation of SREBP1c-mediated de novo lipogenesis. Our data suggest that OLZ induces lipid accumulation in both plasma and liver, and Sim ameliorates OLZ-induced lipid metabolic dysfunction through its effects on mTOR signaling via reducing SREBP1c activation and the downregulation of gene expression involved in lipogenesis. These data provide a new insight into the prevention of metabolic side effects induced by antipsychotic drugs.
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