Search

Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced concentration of plasma triacylglycerols (TAG) but the mechanisms are not fully clarified. Stearoyl-CoA desaturase-1 (SCD1) activity, governing TAG synthesis, is affected by n-3 fatty acids. Peripheral blood mononuclear cells (PBMC) display expression of genes involved in lipid metabolism. The aim of the present study was to estimate whether intake of lean and fatty fish would influence n-3 fatty acids composition in plasma phospholipids (PL), serum TAG, 18:1n-9/18:0 ratio in plasma PL, as well as PBMC gene expression of SCD1 and fatty acid synthase (FAS). Healthy males and females (n = 30), aged 20-40, consumed either 150 g of cod, salmon, or potato (control) daily for 15 days. During intervention docosahexaenoic acid (DHA, 22:6n-3) increased in the cod group (P < 0.05), while TAG concentration decreased (P < 0.05). In the salmon group both eicosapentaenoic acid (EPA, 20:5n-3) and DHA increased (P < 0.05) whereas TAG concentration and the 18:1n-9/18:0 ratio decreased (P < 0.05). Reduction of the 18:1n-9/18:0 ratio was associated with a corresponding lowering of TAG (P < 0.05) and an increase in EPA and DHA (P < 0.05). The mRNA levels of SCD1 and FAS in PBMC were not significantly altered after intake of cod or salmon when compared with the control group. In conclusion, both lean and fatty fish may lower TAG, possibly by reducing the 18:1n-9/18:0 ratio related to allosteric inhibition of SCD1 activity, rather than by influencing the synthesis of enzyme protein.

FA with varying chain lengths and an alpha-methyl group and/or a sulfur in the beta-position were tested as peroxisome proliferator-activated receptor (PPAR)alpha, -delta(beta), and -gamma ligands by transient transfection in COS-1 cells using chimeric receptor expression plasmids, containing cDNAs encoding the ligand-binding domain of PPARalpha, -delta, and -gamma. For PPARalpha, an increasing activation was found with increasing chain length of the sulfur-substituted FA up to C14-S acetic acid (tetradecylthioacetic acid = TTA). The derivatives were poor, and nonsignificant, activators of PPARdelta. For PPARgamma, activation increased with increasing chain length up to C16-S acetic acid. A methyl group was introduced in the alpha-position of palmitic acid, TTA, EPA, DHA, cis9,trans11 CLA, and trans10,cis12 CLA. An increased activation of PPARalpha was obtained for the alpha-methyl derivatives compared with the unmethylated FA. This increase also resulted in increased expression of the two PPARalpha target genes acyl-CoA oxidase and liver FA-binding protein for alpha-methyl TTA, alpha-methyl EPA, and alpha-methyl DHA. Decreased or altered metabolism of these derivatives in the cells cannot be excluded. In conclusion, saturated FA with sulfur in the beta-position and increasing carbon chain length from C9-S acetic acid to C14-S acetic acid have increasing effects as activators of PPARalpha and -gamma in transfection assays. Furthermore, alpha-methyl FA derivatives of a saturated natural FA (palmitic acid), a sulfur-substituted FA (TTA), and PUFA (EPA, DHA, c9,t11 CLA, and t10,c12 CLA) are stronger PPARalpha activators than the unmethylated compounds.

6,9,12,15,18-Heneicosapentaenoic acid (21:5n-3) (HPA), present in small amounts in fish oils, has been prepared by chemical elongation of eicosapentaenoic acid (EPA) and its biological properties compared with EPA and docosahexaenoic acid (DHA). All the double bonds of HPA are displaced one carbon away from the carboxyl group when compared to EPA. HPA is incorporated into phospholipids and into triacylglycerol in cell culture to a similar extent as EPA and DHA. HPA is a stronger inhibitor of the conversion of alpha-linoleic acid and dihomo-gamma-linolenic acid to arachidonic acid (AA) in hepatoma cells than are EPA, DHA, and AA. HPA is a poor substrate for prostaglandin H synthase and for 5-lipoxygenase, but it inactivates prostaglandin H synthase as rapidly as do AA, EPA, and DHA. HPA inhibits thromboxane synthesis in isolated platelets as efficiently as EPA. EPA, HPA, and DHA are all weak inducers of acyl-CoA oxidase in hepatoma cells. Therefore, since fish oils contain only small amounts of HPA, it is unlikely that this fatty acid is of particular significance for the biological effects of these oils, possibly with the exception that it is a strong inhibitor of AA synthesis.