The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics.
Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether 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.
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Zsuzsanna
Z
Literáti-Nagy
Kálmán
K
Tory
Botond
B
Literáti-Nagy
Attila
A
Kolonics
Zsolt
Z
Török
Imre
I
Gombos
Gábor
G
Balogh
László
L
Vígh
Ibolya
I
Horváth
József
J
Mandl
Balázs
B
Sümegi
Philip L
PL
Hooper
László
L
Vígh
D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D050884:HSP72 Heat-Shock Proteins; D007004:Hypoglycemic Agents; D010091:Oximes; D010880:Piperidines; C405586:BGP 15