title: Transcription profiling in rat liver in response to dietary docosahexaenoic acid implicates stearoyl-coenzyme a desaturase as a nutritional target for lipid lowering.
abstract: The gene expression profile in response to dietary docosahexaenoic acid rich oil for 6 wk was analyzed in the livers of male Sprague-Dawley rats to identify genes whose expression was regulated by dietary modification and correlated with serum lipid changes. Such genes may represent targets for intervention into cardiovascular health using nutraceuticals. High density glass microarrays containing approximately 7800 cloned expressed sequences from rat were used to identify those genes that responded to dietary long chain (n-3) fatty acids. In general, dietary long chain (n-3) fatty acids exhibited statistically significant lipid-lowering effects similar to a pharmaceutical alternative, fenofibrate, but showed narrower effects on the transcription of most of the genes assayed. The transcription patterns confirmed that the expression of several key genes involved in cholesterol metabolism, fatty acid beta-oxidation and lipogenesis was affected. These analyses indicated that stearoyl-coenzyme A (Delta9) desaturase, a key enzyme involved in the regulation of triglyceride biosynthesis and secretion, is a potential target for nutritional intervention for hyperlipidemia and cardiovascular health. In addition these results suggested that regulation of the farnesoid X receptor may be a key nutritionally regulated mediator of serum lipid changes. A nutritional product concept based on a convenient dietary aid demonstrated comparable efficacy with less spurious gene regulation than a pharmaceutical alternative.
authors.affiliation: Nutrition and Consumer Sector, Pharmacia Corporation, St. Louis, MO 63167, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kramer
authors.forename: John
authors.initials: J
authors.lastname: LeDeaux
authors.forename: Dustie
authors.initials: D
authors.lastname: Butteiger
authors.forename: Tracy
authors.initials: T
authors.lastname: Young
authors.forename: Carolyn
authors.initials: C
authors.lastname: Crankshaw
authors.forename: Harry
authors.initials: H
authors.lastname: Harlow
authors.forename: Larry
authors.initials: L
authors.lastname: Kier
authors.forename: B Ganesh
authors.initials: BG
authors.lastname: Bhat
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
chemical_list: D004041:Dietary Fats; D000960:Hypolipidemic Agents; D004281:Docosahexaenoic Acids; D013230:Stearoyl-CoA Desaturase; D011345:Fenofibrate