title: Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: positive association with stearoyl-CoA desaturase.
abstract: Psychiatric patients frequently exhibit long-chain n-3 (LCn-3) fatty acid deficits and elevated triglyceride (TAG) production following chronic exposure to second generation antipsychotics (SGAs). Emerging evidence suggests that SGAs and LCn-3 fatty acids have opposing effects on stearoyl-CoA desaturase-1 (SCD1), which plays a pivotal role in TAG biosynthesis. Here we evaluated whether low LCn-3 fatty acid status would augment elevations in rat liver and plasma TAG concentrations following chronic treatment with the SGA risperidone (RSP), and evaluated relationships with hepatic SCD1 expression and activity indices. In rats maintained on the n-3 fatty acid-fortified (control) diet, chronic RSP treatment significantly increased liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios), and significantly increased liver, but not plasma, TAG concentrations. Rats maintained on the n-3 deficient diet exhibited significantly lower liver and erythrocyte LCn-3 fatty acid levels, and associated elevations in LCn-6/LCn-3 ratio. In n-3 deficient rats, RSP-induced elevations in liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios) and liver and plasma TAG concentrations were significantly greater than those observed in RSP-treated controls. Plasma glucose levels were not altered by diet or RSP, and body weight was lower in RSP- and VEH-treated n-3 deficient rats. These preclinical data support the hypothesis that low n-3 fatty acid status exacerbates RSP-induced hepatic steatosis by augmenting SCD1 expression and activity.
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA. robert.mcnamara@uc.edu
authors: Robert K
authors: RK
authors: McNamara
authors: I Jack
authors: IJ
authors: Magrisso
authors: Rylon
authors: R
authors: Hofacer
authors: Ronald
authors: R
authors: Jandacek
authors: Therese
authors: T
authors: Rider
authors: Patrick
authors: P
authors: Tso
authors: Stephen C
authors: SC
authors: Benoit
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D004435:Eating / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D018967:Risperidone / Q000009:adverse effects*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D014280:Triglycerides; D013230:Stearoyl-CoA Desaturase; D018967:Risperidone