ArticleSchizophrenia bulletin2012
Atypical antipsychotics rapidly and inappropriately switch peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents.
Article in Schizophrenia bulletin, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00741026 (A Double-blind, Placebo-controlled, Crossover Study Examining the Acute Effects of Olanzapine on Plasma Leptin, Glucose Tolerance and Free Fatty Acids in Healthy Volunteers), which is not on this map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-blind, Placebo-controlled, Crossover Study Examining the Acute Effects of Olanzapine on Plasma Leptin, Glucose Tolerance and Free Fatty Acids in Healthy Volunteers
Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
- A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.PloS one · 2011Trial
- The Role of Sodium Valproate in Clozapine-Associated Cardiotoxicities: The Importance of Cellular and Systemic Energetics.Cardiovascular toxicology · 2026Review
- Urinary organic acid levels and their associations with clinical characteristics in patients with schizophrenia.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Consensus on the key characteristics of metabolism disruptors.Nature reviews. Endocrinology · 2025Review
- An in-depth exploration of the association between olanzapine, quetiapine and acute pancreatitis based on real-world datasets and network toxicology analysis.Frontiers in pharmacology · 2025Article
- Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.Biomedicines · 2024Article
- Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats.International journal of molecular sciences · 2024Article
- Amylin receptor agonism enhances the effects of liraglutide in protecting against the acute metabolic side effects of olanzapine.iScience · 2024Article
- The anxiolytic drug opipramol inhibits insulin-induced lipogenesis in fat cells and insulin secretion in pancreatic islets.Journal of physiology and biochemistry · 2023Article
- Discovery of a second citric acid cycle complex.Heliyon · 2023Review
- Enhancing endogenous levels of GLP1 dampens acute olanzapine induced perturbations in lipid and glucose metabolism.Frontiers in pharmacology · 2023Article
- Second-generation antipsychotics and metabolic syndrome: a role for mitochondria.Frontiers in psychiatry · 2023Review
- Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: a prospective longitudinal study.Frontiers in pharmacology · 2023Article
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Plasma linoelaidyl carnitine levels positively correlated with symptom improvement in olanzapine-treated first-episode drug-naïve schizophrenia.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Analysis of the clinical characteristics of olanzapine-induced acute pancreatitis.Therapeutic advances in psychopharmacology · 2022Review
- Metabolomic alteration induced by psychotropic drugs: Short-term metabolite profile as a predictor of weight gain evolution.Clinical and translational science · 2021Observational
- Article
- Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse changes in plasma glucose and FFAs is unknown. Chronic treatment with olanzapine, a prototypical, side effect prone atypical antipsychotic, lowered FFA in Sprague-Dawley rats. Olanzapine also lowered plasma FFA acutely, concomitantly impairing in vivo lipolysis and robustly elevating whole-body lipid oxidation. Increased lipid oxidation was evident from accelerated losses of triglycerides after food deprivation or lipid challenge, elevated FFA uptake into most peripheral tissues (∼2-fold) except heart, rises in long-chain 3-hydroxylated acyl-carnitines observed in diabetes, and rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility, were severely blunted by olanzapine. Increased lipid oxidation in muscle could be explained by ∼50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoyltransferase I, malonyl-CoA. This was associated with loss of anapleurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophosphate-activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie the FFA lowering and hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them.
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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.