Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes

Comprehensive Psychoneuroendocrinology

Jan W. Eriksson¹  Maria J. Pereira¹  Assel Sarsenbayeva¹  Morten Thaysen-Andersen²  Priya Dipta³  Miriam Shmuel³  Boaz Tirosh³  Francesca Forno³  Martin Wabitsch⁴  Xesús M. Abalo⁵ 

[1] Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, 751 85 Uppsala, Sweden;Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia;Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, PO Box 12065, 91120, Jerusalem, Israel;Pediatrics and Adolescent Medicine, Ulm University Hospital, Germany;SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden;

关键词: Adipocytes;    Antipsychotics;    Insulin resistance;    Inflammation;    Macrophages;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: Olanzapine and Aripiprazole are widely used second-generation antipsychotic drugs. Olanzapine, more than Aripiprazole, leads to considerable metabolic side effects including obesity and diabetes. While the underlying mechanisms are not fully understood, these side effects are likely associated with mild inflammation in the metabolic organs. An in vitro model that accurately recapitulates the metabolic impact of olanzapine and aripiprazole should be useful to elucidate the underlying mechanisms. Methods: We established co-cultures of matured adipocytes derived from the human SGBS cell line and the THP-1 human monocytic cell-derived or primary macrophages to explore the effects of both drugs on the response to insulin. Results: Olanzapine, but not aripiprazole induced insulin resistance in SGBS adipocytes only when co-cultured with THP-1 or primary macrophages, polarized either into M0, M1 or M2. Noteworthy, M2 macrophages induced olanzapine-dependent insulin resistance in the absence of induction of pro-inflammatory cytokines. Insulin resistance by olanzapine was stronger than induced by high concentration of pro-inflammatory cytokines even in combinations, suggesting the contribution of factors other than the classical inflammatory cytokines to promote insulin resistance in adipocytes by olanzapine. Conclusion: Macrophage/adipocyte co-cultures recapitulate the features of olanzapine-induced insulin resistance and implicate the existence of yet unknown factors in mediating this effect.

【 授权许可】

Unknown