The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics

Zsuzsanna Literáti-Nagy, Kálmán Tory, Botond Literáti-Nagy, Attila Kolonics, Zsolt Török, Imre Gombos, Gábor Balogh, László Vígh, Ibola Horváth, József Mandl, Balázs Sümegi, Philip L. Hooper, László Vígh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the questionwhether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability.

Original languageEnglish
Pages (from-to)517-521
Number of pages5
JournalCell Stress and Chaperones
Volume17
Issue number4
DOIs
Publication statusPublished - Jul 1 2012

Keywords

  • Atypical antipsychotic drugs
  • BGP-15
  • Diabetes
  • HSP
  • HSP inducers
  • HSP72
  • Heat-shock proteins
  • Hydroxylamines
  • Insulin resistance
  • Insulin signaling
  • Membranes
  • Metabolic syndrome
  • Mitochondria
  • Schizophrenia
  • Side effects
  • Therapy
  • Weight gain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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