title: Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: positive association with non-fasting plasma triglyceride levels.
abstract: Although omega-3 (n-3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n-3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 and 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n-3 fatty acid precursor α-linolenic acid (ALA, 18:3n-3) during perinatal development (E0-P100), and a subset of rats fed the ALA- diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). Compared with controls, rats fed the ALA- diet exhibited significantly lower liver long-chain n-3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 and 18:1/18:0 ratios) were significantly greater in n-3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n-3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n-3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n-3 fatty acids repress constitutive triglyceride biosynthesis.
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.
authors: Rylon
authors: R
authors: Hofacer
authors: I Jack
authors: IJ
authors: Magrisso
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
authors: Robert K
authors: RK
authors: McNamara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019518:Postprandial Period; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood*; D014886:Weaning; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D012333:RNA, Messenger; D014280:Triglycerides; D017962:alpha-Linolenic Acid; D013230:Stearoyl-CoA Desaturase