Oils rich in Δ-linolenic acid independently protect against characteristics of fatty liver disease in the Δ6-desaturase null mouse1

Alpha-linolenic acid's (ALA) biological activity is poorly understood and primarily associated with its conversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Delta-6 desaturase (D6D) initiates the metabolism of linoleic acid (LA) and ALA to arachidonic acid, EPA, and DHA, respectively. In this study, D6D knock-out (D6KO) mice were used to evaluate the effects of ALA-rich oils in preventing hepatic steatosis and inflammation. D6KO and wild-type mice were fed 1 of 4 high-fat (14% w/w) diets: (i) lard (LD, 0% n-3 PUFA), (ii) canola oil + ARASCO (CD, 8% ALA), (iii) flax seed oil + ARASCO (FD, 55% ALA), (iv) menhaden oil (MD, 30% EPA/DHA) for 8 or 20 weeks. Livers of D6KO mice consuming CD and FD were depleted of EPA/DHA, and enriched in ALA. Markers of fat accumulation and inflammation were lowest in the MD-fed mice, at 8 and 20 weeks, regardless of genotype. CD- and FD-fed D6KO groups were found to have lower liver lipid accumulation and lower hepatic inflammation relative to the LD-fed mice at 8 weeks. In conclusion, while MD was the most protective, this study shows that ALA can act independently on risk factors associated with the development of fatty liver disease.