Fatty acid desaturase expression in human leucocytes correlates with plasma phospholipid fatty acid status.

Associations between and changes in plasma phospholipid fatty acid (FA) concentrations and expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) in leucocytes were investigated both before and during n-3 FA supplementation for 2 weeks in 20 healthy individuals. Participants were divided into two groups depending on fish intake: one fish meal or less per week and no marine FA supplement (Lowfish, n = 9) and more than one fish meal per week and/or daily oral marine FA supplement (Highfish, n = 11). Before starting supplementation (t = 0), concentrations of n-3 FAs were significantly lower in the Lowfish group compared to the Highfish group. During supplementation in both groups, n-3 FAs increased, whereas n-6 FAs decreased. D5D expression was significantly higher in Lowfish compared to Highfish at t = 0. No difference in D6D or D9D expression was observed. D5D expression was inversely correlated with EPA, DPA, DHA and total n-3 FA, and positively correlated with the ratio total n-6 FA/total n-3 FA at t = 0. Expression of D5D in the Lowfish group as well as D6D in both groups significantly decreased relative to the expression at t = 0 during the first day of supplement. PUFA concentration was generally predicted by its precursor FA and D5D or D6D expression. The correlations mentioned disappeared after 2 weeks of supplementation. This indicates that steady-state FA desaturase expression is associated with plasma phospholipid FA composition. Whether leucocyte desaturase expression may have potential as a marker of PUFA status merits further investigation.

DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis.

Polyunsaturated fatty acids (PUFAs) are normal constituents of the diet, but have properties different from other fatty acids (e.g., through generation of signaling molecules). N-3 PUFAs reduce cancer cell growth, but no unified mechanism has been identified. We show that docosahexaenoic acid (DHA; 22:6 n-3) causes extensive changes in gene expression patterns at mRNA level in the colon cancer cell line SW620. Early changes include unfolded protein response (UPR) and increased levels of phosphorylated eIF2alpha as verified at protein level. The latter is considered a hallmark of endoplasmic reticulum (ER) stress and is abundantly present already after 3 h. It may coordinate many of the downstream changes observed, including signaling pathways for cell cycle arrest/apoptosis, calcium homeostasis, cholesterol metabolism, ubiquitination, and proteasomal degradation. Also, eicosapentaenoic acid (EPA), but not oleic acid (OA), induced key mediators of ER stress and UPR at protein level. Accumulation of esterified cholesterol was not compensated for by increased total levels of cholesterol, and mRNAs for cholesterol biosynthesis as well as de novo synthesis of cholesterol were reduced. These results suggest that cytotoxic effects of DHA are associated with signaling pathways involving lipid metabolism and ER stress.