Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-CoA desaturase activity

SCHIZOPHRENIA RESEARCH

卷:129

Article

McNamara, Robert K.¹  Jandacek, Ronald²  Rider, Therese²  Tso, Patrick²  Cole-Strauss, Allyson¹  Lipton, Jack W.¹ 

[1] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45219 USA

[2] Univ Cincinnati, Dept Pathol, Cincinnati, OH 45237 USA

关键词: Stearoyl-CoA desaturase-1;    Oleic acid;    Desaturation index;    Triglycerides;    Glucose;    Insulin;    Liver;    Erythrocytes;    Postprandial;    Rat;   

DOI  :  10.1016/j.schres.2011.03.016

来源: Elsevier

【 摘 要 】

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6 mg/kg/d), paliperidone (1.5, 3, and 6 mg/kg/d), olanzapine (2.5, 5, and 10 mg/kg/d), quetiapine (5, 10, and 20 mg/kg/d), haloperidol (1, and 3 mg/kg/d) or vehicle through their drinking water for 40 days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n = 122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. (C) 2011 Elsevier B.V. All rights reserved.

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