Metabolic liver disease, also known as non-alcoholic fatty liver disease (NAFLD) is a growing global health problem that is most often linked to obesity and diabetes. NAFLD is progressive and the more serious form (NASH) is a leading cause of liver transplantation world-wide, and its incidence is rapidly growing worldwide. NAFLD/NASH is an independent risk factor for cardiovascular disease and chronic kidney disease. Atypical antipsychotic medications (AA) are widely prescribed for the treatment of several psychiatric disorders, including schizophrenia, bipolar disorder and treatment-resistant depression. Antipsychotic drugs cause myriad metabolic and endocrine side effects, including systemic inflammation, weight gain, dyslipidemia and insulin resistance, all of which are associated with increased incidence of NAFLD. NAFLD is highly prevalent in patients with mental illness, and AA have been shown to increase incidence of NAFLD pre-clinically and clinically. However, the underlying mechanisms are not well understood.
UNECOM researchers, Dr. Meghan May, Dr. Karen Houseknecht, Deborah Barlow, BS and student doctor Radwa Ibrahim (COM ’23) teamed up to evaluate drug-associated mechanisms using a multi-omic approach, whereby they profiled expression of proteins in livers from animals treated with clinically relevant doses of antipsychotic medications and compared these findings to clinical samples from patients treated with AA medications. The published study reports novel findings that AA medications olanzapine, risperidone and aripiprazole caused changes in proteins and regulatory pathways involved in the development of NAFLD/NASH, as well as pathways regulating iron accumulation, systemic inflammation and dyslipidemia.
The manuscript, entitled: Mechanisms Underlying Antipsychotic-Induced NAFLD and Iron Dysregulation: A Multi-Omic Approach was published in Biomedicines 2022, 10(6), 1225; https://doi.org/10.3390/biomedicines10061225