Endogenous omega-3 long-chain fatty acid biosynthesis from alpha-linolenic acid is affected by substrate levels, gene expression, and product inhibition†
Previous studies have suggested that dietary alpha-linolenic acid (ALA) increases the levels of omega-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs) in vivo, but the conversion procedure and the genes involved remain poorly understood. In the present work, we designed diets containing various concentrations of ALA and eicosapentaenoic acid (EPA) to feed to mice. Dietary ALA increased the ALA levels in the body in a linear manner and also increased the ω-3 LC-PUFA concentration, but higher ALA intake (above 5%) had no additional effect on ω-3 LC-PUFA levels in vivo. Dietary ALA at a moderate level increased the expression of genes such as Fads1, Fads2, and Elovl5, but higher levels of dietary ALA (above 5%) inhibited their expression in the liver. Further studies demonstrated that the converted EPA could also inhibit the expression of these genes in a concentration-dependent manner, which illustrated that Fads1, Fads2, and Elovl5 were the key genes involved in the conversion of ALA to ω-3 LC-PUFAs. Endogenous ω-3 LC-PUFA biosynthesis from ALA was affected by substrate level, gene expression, and product inhibition.