Influence of genotype on the modulation of gene and protein expression by n-3 LC-PUFA in rats

It is becoming increasingly apparent that responsiveness to dietary fat composition is heterogeneous and dependent on the genetic make-up of the individual. The aim of this study was to evidence a genotype-related differential effect of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on the modulation of hepatic genes involved in cholesterol metabolism. Fourteen spontaneously hypertensive (SH) rats, which present a naturally occurring variation in the gene encoding for sterol responsive element binding protein 1 (SREBP-1), contributing to their inherited variation in lipid metabolism, and 14 Wistar-Kyoto (WK) rats were fed a control diet or an n-3 LC-PUFA enriched diet for 90 days. Plasma lipid profile, total lipid fatty acid composition in plasma and liver, and the expression of SREBP-1 and 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, low-density lipoprotein receptor, and acyl-CoA:cholesterol acyltransferase 2 encoding genes and proteins were determined. The positive effect of the enriched diet on the serum lipid profile, particularly on total cholesterol and triglyceride level, was clearly evidenced in both WK and SH rats, but n-3 LC-PUFA acted through a different modulation of gene and protein expression that appeared related to the genetic background. Our study evidences a different transcriptional effect of specific nutrients related to genetic variants.