ArticleSchizophrenia bulletin2014
Second-generation antipsychotics cause a rapid switch to fat oxidation that is required for survival in C57BL/6J mice.
Article in Schizophrenia bulletin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Fenofibrate Protects Against Antipsychotic-Induced Hyperglycemia Through Weight Loss and FGF21 Dependent Mechanisms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Amylin receptor agonism enhances the effects of liraglutide in protecting against the acute metabolic side effects of olanzapine.iScience · 2024Article
- Discovery of a second citric acid cycle complex.Heliyon · 2023Review
- Second-generation antipsychotics and metabolic syndrome: a role for mitochondria.Frontiers in psychiatry · 2023Review
- Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice.Metabolites · 2022Article
- Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers.Brain sciences · 2022Article
- Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation.Frontiers in psychiatry · 2022Article
- Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells.International journal of molecular sciences · 2021Article
- Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.International journal of molecular sciences · 2021Review
- Article
- Exploring mechanisms of increased cardiovascular disease risk with antipsychotic medications: Risperidone alters the cardiac proteomic signature in mice.Pharmacological research · 2020Article
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.Metabolic brain disease · 2018Article
- Effects ofEvidence-based complementary and alternative medicine : eCAM · 2018Article
- Antipsychotic Drugs: From Receptor-binding Profiles to Metabolic Side Effects.Current neuropharmacology · 2018Review
- H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.Metabolic brain disease · 2016Article
- RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.PloS one · 2015Article
- Some side effects and effcts on physical activity of second-generation antipsychotics: A study in children and adolescents.Advanced biomedical research · 2014Article
- Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Some second-generation antipsychotics (SGAs) increase insulin resistance and fat oxidation, but counter intuitively they do not activate lipolysis. This seems unsustainable for meeting energy demands. Here, we measured dose-dependent effects of SGAs on rates of oxygen consumption (VO2), respiratory exchange ratio (RER), and physical activity in C57BL/6J mice. The role of H1-histamine receptors and consequences of blocking fat oxidation were also examined. Olanzapine, risperidone, and clozapine (2.5-10mg/kg) elicited rapid drops in dark-cycle RER (~0.7) within minutes, whereas aripiprazole exerted only modest changes. Higher doses of olanzapine decreased VO2, and this was associated with accumulation of glucose in plasma. Clozapine and risperidone also lowered VO2, in contrast to aripiprazole, whereas all decreased physical activity. Astemizole and terfenadine had no significant effects on RER, VO2, or physical activity. The VO2 and RER effects appear independent of sedation/physical activity or H1-receptors. CPT-1 inhibitors can enhance muscle glucose utilization and prevent fat oxidation. However, after etomoxir (2 × 30 mg/kg), a low dose of olanzapine that did not significantly affect VO2 by itself caused precipitous drops in VO2 and body temperature, leading to death within hours or a moribund state requiring euthanasia. One 30 mg/kg dose of either etomoxir or 2-tetradecylglycidate followed by olanzapine, risperidone, or clozapine, but not aripiprazole, dramatically lowered VO2 and body temperature. Thus, mice treated with some SGAs shift their fuel utilization to mostly fat but are unable to either switch back to glucose or meet their energy demands when either higher doses are used or when fat oxidation is blocked.
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