Antipsychotics Promote Metabolic Disorders Disrupting Cellular Lipid Metabolism and Trafficking

Research output: Contribution to journalReview article

Abstract

Antipsychotics frequently cause obesity and related metabolic disorders that current psychopharmacological/endocrinological theories do not explain consistently. An integrative/alternative theory implies metabolic alterations happening at the cellular level. Many observations in vitro and in vivo, and pivotal observations in humans, point towards chemical properties of antipsychotics, independent of receptor binding characteristics. Being amphiphilic weak bases, antipsychotics can disrupt lysosomal function, affecting cholesterol trafficking; moreover, by chemical mimicry, antipsychotics can inhibit cholesterol biosynthesis. These two molecular adverse effects may trigger a cascade of transcriptional and biochemical events, ultimately reducing available cholesterol while increasing cholesterol precursors and fatty acids. The macroscopic manifestation of these molecular alterations includes decreased high-density lipoprotein and increased very low-density lipoprotein and triglycerides that may translate into obesity and related metabolic disorders.

Original languageEnglish
Pages (from-to)189-210
Number of pages22
JournalTrends in Endocrinology and Metabolism
Volume30
Issue number3
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • antipsychotic drugs
  • cholesterol
  • lysosomal trapping
  • metabolism
  • SREBP
  • weight

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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