Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state.
Second-generation antipsychotics are widely used in the treatment of all forms of psychoses, but they often produce undesirable side effects, among which are weight gain and other elements of metabolic syndrome. The mechanisms of these adverse effects are not known. The liver and adipose tissue are the principal candidate organs implicated in the development of antipsychotic-induced metabolic adverse effects. The present study investigated in the rat the effects on liver and white adipose tissue of a chronic treatment (46 days) with olanzapine 2 mg/kg or haloperidol 1 mg/kg, as compared with a control solution. In the liver, the expression of key genes involved in glucose transport and lipid metabolism and of regulatory transcription factors, as well as the TNFalpha gene, was not altered in response to either antipsychotic. Similarly, key genes involved in glucose transport and lipid metabolism were not changed in adipose tissue. However, the white adipose tissue was inflammatory in olanzapine-treated rats, with extensive macrophage infiltration and a significant increase in TNFalpha expression. In the plasma, TNFalpha and IL-1beta concentrations were slightly elevated. Chronic olanzapine treatment therefore produces a low-grade inflammatory state, likely initiated in the adipose tissue. Such an inflammatory state is known to be associated with an increased risk of insulin-resistance and cardiovascular diseases. This antipsychotic-induced inflammatory syndrome may participate in the inflammatory syndrome often observed in patients with schizophrenia. The strong and rather selective effect of olanzapine on TNFalpha expression may open new therapeutic opportunities for the prevention of olanzapine-induced metabolic abnormalities.
Victoriano
Montserrat
M
UMR914, INRA, Physiologie de la Nutrition et du Comportement Alimentaire, 16 rue Claude Bernard, F-75005 Paris, France.
de Beaurepaire
Renaud
R
Naour
Nadia
N
Guerre-Millo
Michèle
M
Quignard-Boulangé
Annie
A
Huneau
Jean-François
JF
Mathé
Véronique
V
Tomé
Daniel
D
Hermier
Dominique
D
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007118:Immunoassay; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014150:Antipsychotic Agents; D016207:Cytokines; D020738:Leptin; D001569:Benzodiazepines; D005947:Glucose; D006220:Haloperidol; D000077152:Olanzapine