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.