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Alterations of adipose tissue phenotype and gene expression in olanzapine treated rats
Author(s) -
Victoriano Montserrat,
Beaurepaire Renaud,
Naour Nadia,
GuerreMillo Michele,
QuignardBoulange Annie,
Huneau JeanFrançois,
Mathé Véronique,
Tomé Daniel,
Hermier Dominique
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.547.2
Subject(s) - adipose tissue , endocrinology , medicine , inflammation , adipokine , adipocyte , olanzapine , haloperidol , cd68 , gene expression , lipid metabolism , adipose tissue macrophages , weight gain , phenotype , brown adipose tissue , biology , white adipose tissue , obesity , body weight , immunohistochemistry , dopamine , gene , insulin resistance , schizophrenia (object oriented programming) , biochemistry , psychiatry
Contrary to typical antipsychotics (AP) such as haloperidol (HA), certain atypical antipsychotic (AAP), such as olanzapine (OL) induce a weight gain associated with increased visceral adipose tissue (VAT). A specific increase in VAT was reported in a model of chronically OL‐treated rats, without hyperphagia or increased body weight (Victoriano et al., 2009). This suggests a direct effect of AAP on AT phenotype and on gene expression of proteins involved in metabolic or secretory functions. Thus, male rats were given, for 6 wks, diets containing OL (2mg/kg), HA (1mg/kg) or the vehicle (control group, CO) (n=6). The epididymal AT proportion was the highest in OL rats (1.63% vs 1.44% in CO and HA rats), without adipocyte hypertrophy. The % of CD68+ cells (markers of macrophage infiltration) was 2.8 in OL rats, 0.07 in HA rats and 0 in CO rats. The expression of genes controlling lipid metabolism was not modified. Among adipokines, only gene expression of TNFα; was modified, its ARNm being twice higher in OL than in CO and HA rats, and indicating a local low grade inflammation. This suggests that a local action of AAP on the AT results in the recruitment of macrophages. The increase expression of TNFα; by these macrophages may contribute to impair insulin sensitivity, resulting in the metabolic complications of AAP treatment. The occurrence of this inflammatory status has now to be investigated in human patients.