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Nutrient-Gene Interactions

Transcription Profiling in Rat Liver in Response to Dietary Docosahexaenoic Acid Implicates Stearoyl-Coenzyme A Desaturase as a Nutritional Target for Lipid Lowering

Nutrition and Consumer Sector, Pharmacia Corporation, St. Louis, MO 63167 and ^* Monsanto Corporation, St. Louis, MO 63167

²To whom correspondence should be addressed. E-mail: b.ganesh.bhat{at}pharmacia.com.

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 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 ß-oxidation and lipogenesis was affected. These analyses indicated that stearoyl-coenzyme A (9) 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.

KEY WORDS: • (n-3) fatty acids • nutraceuticals • cardiovascular • gene transcription

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