Effects of the second-generation antipsychotic drugs aripiprazole and olanzapine on human adipocyte differentiation

• Published in: Molecular and cellular endocrinology Vol. 561; p. 111828
• Main Authors: Vranic, Milica, Ahmed, Fozia, Hetty, Susanne, Sarsenbayeva, Assel, Ferreira, Vitor, Fanni, Giovanni, Valverde, Ángela M., Eriksson, Jan W., Pereira, Maria J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 05.02.2023
• Subjects: Adipocyte; Adipocytes - metabolism; Adipogenesis; Antipsychotic Agents - adverse effects; Aripiprazole; Aripiprazole - metabolism; Aripiprazole - pharmacology; Diabetes Mellitus, Type 2 - metabolism; Humans; Olanzapine; Olanzapine - metabolism; Olanzapine - pharmacology; Piperazines - metabolism; Piperazines - pharmacology; Piperazines - therapeutic use; Adipocyte; Olanzapine; Aripiprazole; Adipogenesis
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2022.111828

Second-generation antipsychotics (SGAs), used as the cornerstone treatment for schizophrenia and other mental disorders, can cause adverse metabolic effects (e.g. obesity and type 2 diabetes). We investigated the effects of SGAs on adipocyte differentiation and metabolism. The presence of therapeutic concentrations of aripiprazole (ARI) or its active metabolite dehydroaripiprazole (DARI) during human adipocyte differentiation impaired adipocyte glucose uptake while the expression of gene markers of fatty acid oxidation were increased. Additionally, the use of a supra-therapeutic concentration of ARI inhibited adipocyte differentiation. Furthermore, olanzapine (OLA), a highly obesogenic SGA, directly increased leptin gene expression but did not affect adipocyte differentiation and metabolism. These molecular insights are novel, and suggest that ARI, but not OLA, may directly act via alterations in adipocyte differentiation and potentially by causing a switch from glucose to lipid utilization in human adipocytes. Additionally, SGAs may effect crosstalk with other organs, such as the brain, to exert their adverse metabolic effects. •Aripiprazole (10 μM), but not olanzapine, inhibits adipogenesis.•Aripiprazole (1–2 μM) reduces adipocyte glucose uptake independently of adipogenesis.•Aripiprazole increases expression of lipid oxidation genes in differentiated adipocytes.•Olanzapine and aripiprazole increase leptin expression in differentiated adipocytes.