ArticleThe pharmacogenomics journal2010
Antipsychotic drugs upregulate lipogenic gene expression by disrupting intracellular trafficking of lipoprotein-derived cholesterol.
Article in The pharmacogenomics journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Weight gain under antipsychotic and mood stabilizing treatment: a narrative review about mechanisms and future options.International journal of bipolar disorders · 2025Review
- Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.Acta pharmacologica Sinica · 2024Article
- Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients.Translational psychiatry · 2024Article
- STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death.Cancers · 2022Article
- The Association Between Antipsychotics and Weight Gain and the Potential Role of Metformin Concomitant Use: A Retrospective Cohort Study.Frontiers in psychiatry · 2022Article
- Article
- The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo.International journal of molecular sciences · 2021Article
- Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance.Cancer cell international · 2021Article
- Key role for lipids in cognitive symptoms of schizophrenia.Translational psychiatry · 2020Article
- Cancer and the Dopamine DThe Journal of pharmacology and experimental therapeutics · 2019Review
- Article
- The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization.Molecules (Basel, Switzerland) · 2018Article
- Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.Metabolic brain disease · 2018Article
- Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine.BMC pharmacology & toxicology · 2017Article
- Neuronal Activity-Induced Sterol Regulatory Element Binding Protein-1 (SREBP1) is Disrupted in Dysbindin-Null Mice-Potential Link to Cognitive Impairment in Schizophrenia.Molecular neurobiology · 2017Article
- Antipsychotic-associated weight gain: management strategies and impact on treatment adherence.Neuropsychiatric disease and treatment · 2017Review
- Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα-SREBP Pathway in 3T3-L1 Cells.International journal of molecular sciences · 2016Article
- First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro.International journal of molecular sciences · 2016Article
- Simultaneous Use of Intravenous Lipid Emulsion and Plasma Exchange Therapies in Multiple Drug Toxicity.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2016Article
- Clinically used selective oestrogen receptor modulators increase LDL receptor activity in primary human lymphocytes.British journal of pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antipsychotic drugs (APDs) have been reported to induce lipogenic genes. This has been proposed to contribute to their efficacy in treating schizophrenia and other psychiatric disorders, as well as the metabolic side effects often associated with these drugs. The precise mechanism for the lipogenic effects of APDs is unknown, but is believed to involve increased activation of the lipogenic transcription factors, such as sterol regulatory element binding proteins (SREBPs). In a series of experiments in a model cell line, we found that a panel of typical and atypical APDs inhibited transport of lipoprotein-derived cholesterol to the endoplasmic reticulum (ER), which houses the cholesterol homeostatic machinery. APDs belong to the class of cationic amphiphiles and as has been shown for other amphiphiles, caused lipoprotein-derived cholesterol to accumulate intracellularly, preventing it from being esterified in the ER and suppressing SREBP activation. APDs did not activate the liver X receptor, another transcription factor involved in lipogenesis. However, these drugs markedly reduced cholesterol synthesis. This paradoxical result indicates that the upregulation of SREBP-target genes by APDs may not translate to increased cellular cholesterol levels. In conclusion, we have determined that APDs disrupt intracellular trafficking and synthesis of cholesterol, which may have important clinical ramifications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.