ArticleThe Journal of pharmacology and experimental therapeutics2013
Olanzapine activates hepatic mammalian target of rapamycin: new mechanistic insight into metabolic dysregulation with atypical antipsychotic drugs.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients.Clinical drug investigation · 2016Trial
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Modulation of Leucine Sensors to Mitigate Antipsychotics-Induced Metabolic Syndrome: A New Vista.ACS pharmacology & translational science · 2024Article
- Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients.Translational psychiatry · 2024Article
- Comprehensive Two-Dimensional Gas Chromatography as a Bioanalytical Platform for Drug Discovery and Analysis.Pharmaceutics · 2023Review
- Second-generation antipsychotics and metabolic syndrome: a role for mitochondria.Frontiers in psychiatry · 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
- Long-term effects of adolescent exposure to olanzapine in C57BL/6 J mice and the impact of dietary fish oil supplementation.Psychopharmacology · 2022Article
- The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity.Life (Basel, Switzerland) · 2022Article
- Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.Translational psychiatry · 2022Review
- Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine.Frontiers in pharmacology · 2022Article
- Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate-Activated Protein Kinase, Causing Sarcopenia in Alcohol-Associated Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells.International journal of molecular sciences · 2021Article
- Olanzapine-induced liver injury in mice: aggravation by high-fat diet and protection with sulforaphane.The Journal of nutritional biochemistry · 2020Article
- Mechanisms of Action of Autophagy Modulators Dissected by Quantitative Systems Pharmacology Analysis.International journal of molecular sciences · 2020Article
- Rapamycin attenuates liver injury caused by vinyl chloride metabolite chloroethanol and lipopolysaccharide in mice.Toxicology and applied pharmacology · 2019Article
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Olanzapine induced autophagy through suppression of NF-κB activation in human glioma cells.CNS neuroscience & therapeutics · 2019Article
- Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway.Acta pharmacologica Sinica · 2019Article
- Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1.Redox biology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Olanzapine (OLZ), an effective treatment of schizophrenia and other disorders, causes weight gain and metabolic syndrome. Most studies to date have focused on the potential effects of OLZ on the central nervous system's mediation of weight; however, peripheral changes in liver or other key metabolic organs may also play a role in the systemic effects of OLZ. Thus, the purpose of this study was to investigate the effects of OLZ on hepatic metabolism in a mouse model of OLZ exposure. Female C57Bl/6J mice were administered OLZ (8 mg/kg per day) or vehicle subcutaneously by osmotic minipumps for 28 days. Liver and plasma were taken at sacrifice for biochemical analyses and for comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry metabolomics analysis. OLZ increased body weight, fat pad mass, and liver-to-body weight ratio without commensurate increase in food consumption, indicating that OLZ altered energy expenditure. Expression and biochemical analyses indicated that OLZ induced anaerobic glycolysis and caused a pseudo-fasted state, which depleted hepatic glycogen reserves. OLZ caused similar effects in cultured HepG2 cells, as determined by Seahorse analysis. Metabolomic analysis indicated that OLZ increased hepatic concentrations of amino acids that can alter metabolism via the mTOR pathway; indeed, hepatic mTOR signaling was robustly increased by OLZ. Interestingly, OLZ concomitantly activated AMP-activated protein kinase (AMPK) signaling. Taken together, these data suggest that disturbances in glucose and lipid metabolism caused by OLZ in liver may be mediated, at least in part, via simultaneous activation of both catabolic (AMPK) and anabolic (mammalian target of rapamycin) pathways, which yields new insight into the metabolic side effects of this drug.
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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.