Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice
Patients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistanc...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9362 |
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| author | Bahman Rostama Megan Beauchemin Celeste Bouchard Elizabeth Bernier Calvin P. H. Vary Meghan May Karen L. Houseknecht |
| author_facet | Bahman Rostama Megan Beauchemin Celeste Bouchard Elizabeth Bernier Calvin P. H. Vary Meghan May Karen L. Houseknecht |
| author_sort | Bahman Rostama |
| collection | DOAJ |
| description | Patients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistance, both of which are induced by several antipsychotic medications. NAFLD is considered an independent risk factor for cardiovascular disease, the leading cause of death for patients with severe mental illness. Although the clinical literature clearly defines increased risk of NAFLD with antipsychotic therapy, the underlying mechanisms are not understood. Given the complexity of the disorder as well as the complex pharmacology associated with atypical antipsychotic (AA) medications, we chose to use a proteomic approach in healthy mice treated with a low dose of risperidone (RIS) or olanzapine (OLAN) for 28 days to determine effects on development of NAFLD and to identify pathways impacted by AA medications, while removing confounding intrinsic effects of mental illness. Both AA drugs caused development of steatosis in comparison with vehicle controls (<i>p</i> < 0.01) and affected multiple pathways relating to energy metabolism, NAFLD, and immune function. AA-associated alteration in autonomic function appears to be a unifying theme in the regulation of hepatic pathology. |
| first_indexed | 2024-03-10T14:13:28Z |
| format | Article |
| id | doaj.art-343ae61215514fdebb67689295c7b697 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:13:28Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-343ae61215514fdebb67689295c7b6972023-11-20T23:56:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124936210.3390/ijms21249362Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in MiceBahman Rostama0Megan Beauchemin1Celeste Bouchard2Elizabeth Bernier3Calvin P. H. Vary4Meghan May5Karen L. Houseknecht6Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USADepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USADepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USADepartment of Psychology, University of Southern Maine, Portland, ME 04103, USACenter for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USADepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USADepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USAPatients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistance, both of which are induced by several antipsychotic medications. NAFLD is considered an independent risk factor for cardiovascular disease, the leading cause of death for patients with severe mental illness. Although the clinical literature clearly defines increased risk of NAFLD with antipsychotic therapy, the underlying mechanisms are not understood. Given the complexity of the disorder as well as the complex pharmacology associated with atypical antipsychotic (AA) medications, we chose to use a proteomic approach in healthy mice treated with a low dose of risperidone (RIS) or olanzapine (OLAN) for 28 days to determine effects on development of NAFLD and to identify pathways impacted by AA medications, while removing confounding intrinsic effects of mental illness. Both AA drugs caused development of steatosis in comparison with vehicle controls (<i>p</i> < 0.01) and affected multiple pathways relating to energy metabolism, NAFLD, and immune function. AA-associated alteration in autonomic function appears to be a unifying theme in the regulation of hepatic pathology.https://www.mdpi.com/1422-0067/21/24/9362antipsychoticliverproteomeenergy metabolismnonalcoholic fatty liver diseasesteatosis |
| spellingShingle | Bahman Rostama Megan Beauchemin Celeste Bouchard Elizabeth Bernier Calvin P. H. Vary Meghan May Karen L. Houseknecht 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 antipsychotic liver proteome energy metabolism nonalcoholic fatty liver disease steatosis |
| title | Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice |
| title_full | Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice |
| title_fullStr | Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice |
| title_full_unstemmed | Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice |
| title_short | Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice |
| title_sort | understanding mechanisms underlying non alcoholic fatty liver disease nafld in mental illness risperidone and olanzapine alter the hepatic proteomic signature in mice |
| topic | antipsychotic liver proteome energy metabolism nonalcoholic fatty liver disease steatosis |
| url | https://www.mdpi.com/1422-0067/21/24/9362 |
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