Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status

Abstract This study investigated the effects of perinatal dietary omega-3 ( n -3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n -3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n -3 fatty acid repletion would normalize this response. Adult rats fed the n -3–free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LC n -3 fatty acid composition and reciprocal elevations in LC omega-6 ( n -6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2 , but not Fads1 , Elovl2 , or Elovl5 , mRNA expression was significantly greater in n- 3–deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3 n -6/18:2 n -6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3 n -6/18:2 n -6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LC n -6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n -3 fatty acids.