Omega 3 long chain fatty acid synthesis is regulated more by substrate levels than gene expression.

Key Findings:

The regulation of tissue LCPUFA levels when dietary ALA levels are similar to what could be expected in human diets was explored in rats. When diets contained very low levels of PUFA (0.4% en), the expressions of FADS2 and ELOVL2 genes were higher than when diets had increased levels of PUFA diets. These genes code for desaturase and elongase enzymes. Endogenous conversion of dietary ALA into EPA, DPA, and DHA was noted when ALA levels were between 0.2% and 2.8% of en, in conjunction with a sufficient amount of LA (1% en). The association between dietary ALA content and the levels of EPA and DPA generated was essentially linear and for DHA there was a curvilinear relationship with a maximum at 1% en dietary ALA. The diets in which the dietary PUFA level was always above 1.2% en resulted in little or no change in the expression of genes involved in the actions of conversion enzymes. The findings show a direct relationship between dietary ALA and elevated EPA and DPA accumulation in rat plasma and liver. Increasing dietary ALA elevated DHA but only up to a maximum at 1% en ALA. At the levels of dietary PUFA used, omega 3 LCPUFA levels appear to be regulated more by competitive interaction between distinct substrates at different stages of LCPUFA biosynthesis than alterations in the expression of key components of the lipid metabolism and LCPUFA biosynthetic pathway.

ABSTRACT:

The conversion of linoleic acid (LA) and alpha-linolenic acid (ALA) to long chain polyunsaturated fatty acids (LCPUFA) is known to involve desaturation and elongation steps. Although there is evidence that genes for these steps can be regulated by extremes of dietary PUFA, the degree to which there is meaningful regulation of LC PUFA levels in tissues by diet as a result of changes in expression of desaturase and elongase genes is unclear. In this study, we tested the effect of increasing ALA level s in diets of rats from 0.2% to 2.9% energy (en) against a constant LA level (1% en) on plasma and liver phospholipid LC PUFA content together with the expression of hepatic genes involved in PUFA metabolism, the desaturases FADS1 and FADS2, the elongases ELOV2 and ELOV5, and the transcription factors sterol regulatory element-binding protein-1 c (SREBP- 1c) and peroxisome proliferator–activated receptor alpha (PPAR a). The levels of plasma and liver eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) increased in proportion to dietary ALA whereas docosahexaenoic acid (DHA) increased only up to 1% en ALA. A low PUFA (0.4%en) reference diet stimulated the expression of delta 6 desaturase (FADS 2) and elongase 2 (ELOVL2) when compared to higher PUFA diets. There was, however, no difference in the expression of any of the genes in rats, which were fed diets containing between 0.2% en and 2.9% en ALA and mRNA expression was unrelated to tissue/plasma LCPUFA content. These data suggest that the endogenous synthesis of n- 3 LCPU FA from the precursor ALA is regulated independently of changes in the expression of the synthetic enzymes or regulatory transcription factor, and provides evidence that n- 3 LC PUFA synthesis is regulated more by substrate competition for existing enzymes than by an increase in their mRNA expression. (Author`s abstract)