Antipsychotic-induced increase in lipid biosynthesis: activation through inhibition?

Silje Skrede,Vidar Martin Steen,Johan Fern⊘

doi:10.1194/jlr.e034736

Silje Skrede, Vidar Martin Steen + Show 1 more

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https://doi.org/10.1194/jlr.e034736

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Abstract

Antipsychotic-induced increase in lipid biosynthesis: activation through inhibition?

Highlights

Antipsychotic drugs have become indispensable in the treatment of schizophrenia since the introduction of firstgeneration antipsychotics (FGA; e.g., chlorpromazine and haloperidol) in the 1950s
We and others have demonstrated that antipsychotic drugs induce transcriptional activation of cholesterol and fatty acid biosynthesis genes controlled by the SREBP1 and SREBP2 transcription factors [11, 12]
How these apparently divergent in vitro findings may be unified to form a common theory has not yet been sorted out, with respect to their possible role in explaining antipsychotic-induced metabolic adverse effects in the clinical setting. In this issue of Journal of Lipid Research, Canfrán-Duque et al [13] contribute new, interesting data on the effect of antipsychotic drugs on cellular cholesterol biosynthesis and transport, elaborating previous work by others and themselves [6, 14,15,16]. They demonstrate that the FGA haloperidol and the second-generation antipsychotics (SGA) clozapine, risperidone, and ziprasidone reduce de novo cholesterol biosynthesis in three different types of cultured human cells (HepG2, SH-SY5Y, and HL60)

Summary

Introduction

Antipsychotic drugs have become indispensable in the treatment of schizophrenia since the introduction of firstgeneration antipsychotics (FGA; e.g., chlorpromazine and haloperidol) in the 1950s. We and others have demonstrated that antipsychotic drugs induce transcriptional activation of cholesterol and fatty acid biosynthesis genes controlled by the SREBP1 and SREBP2 transcription factors [11, 12]. In this issue of Journal of Lipid Research, Canfrán-Duque et al [13] contribute new, interesting data on the effect of antipsychotic drugs on cellular cholesterol biosynthesis and transport, elaborating previous work by others and themselves [6, 14,15,16].

Results

Conclusion