期刊
SCHIZOPHRENIA RESEARCH
卷 129, 期 1, 页码 66-73出版社
ELSEVIER
DOI: 10.1016/j.schres.2011.03.016
关键词
Stearoyl-CoA desaturase-1; Oleic acid; Desaturation index; Triglycerides; Glucose; Insulin; Liver; Erythrocytes; Postprandial; Rat
类别
资金
- Ortho-McNeil Janssen Pharmaceuticals [R076477SCH0004]
- NIH [MH073704, DK59630, DA017399]
- Ortho-McNeil Janssen Scientific Affairs LLC [R076477SCH0004]
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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