Dataset Information

Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: Relationship with liver delta6-desaturase expression.

ABSTRACT: Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6mg/kg/day), paliperidone (1.5, 3, 6mg/kg/day), olanzapine (2.5, 5, 10mg/kg/day), quetiapine (5, 10, 20mg/kg/day), haloperidol (1, 3mg/kg/day) or vehicle through their drinking water for 40day. Effects on liver Fads1, Fads2, Elovl2, and Elovl5 mRNA expression, plasma indices of n-3 (plasma 22:6/18:3 and 20:5/18:3 ratios) and n-6 (plasma 20:4/18:2 and 20:3/18:2 ratios) biosynthesis, and peripheral (erythrocyte, heart) and central (frontal cortex) membrane PUFA composition were determined. Only risperidone and its metabolite paliperidone significantly and selectively up-regulated liver delta-6 desaturase (Fads2) mRNA expression, and robustly increased plasma indices of n-3 and n-6 fatty acid biosynthesis. In risperidone- and paliperidone-treated rats, plasma indices of n-3 and n-6 fatty acid biosynthesis were all positively correlated with liver Fads2 mRNA expression, but not Fads1, Elovl2, or Elovl5 mRNA expression. All antipsychotics at specific doses increased erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition, and all except quetiapine increased arachidonic acid (AA, 20:4n-6) composition. Risperidone, paliperidone, and olanzapine increased heart DHA and AA composition, and no antipsychotic altered frontal cortex DHA or AA composition. These in vivo data demonstrate that augmentation of PUFA biosynthesis is not common to all antipsychotic medications, and that risperidone and paliperidone uniquely increase delta-6 desaturase (Fads2) mRNA expression and most robustly increase PUFA biosynthesis and peripheral membrane composition.

SUBMITTER: McNamara RK

PROVIDER: S-EPMC3100388 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: Relationship with liver delta6-desaturase expression.

McNamara Robert K RK Jandacek Ronald R Rider Therese T Tso Patrick P Cole-Strauss Allyson A Lipton Jack W JW

Schizophrenia research 20110331 1

Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6mg/kg/day), paliperidone (1.5, 3, 6mg/kg/day), olanzapine (2.5, 5, 10mg/kg/day), quetiapine (5, 10, 20mg/kg/day), haloperidol (1, 3mg/kg/day) or vehicle ...[more]

PMID: 21458237

Similar Datasets

Project description:BackgroundPolyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions.ObjectiveWe explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions.DesignWe studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models.ResultsAfter adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype.ConclusionsCarriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.

Dataset Information

Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: Relationship with liver delta6-desaturase expression.

Publications

Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: Relationship with liver delta6-desaturase expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets