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Conjugated linoleic acid (CLA) and some trans fatty acids (FA) decrease tumor growth and alter tumor and host lipid uptake and storage. The goal of this study was to test the hypothesis that the acute inhibitory effects of CLA isomers and trans FAs on FA transport in tumors and white adipose tissue are mediated via an inhibitory G-protein coupled (GPC), FFA receptor (FFAR). Experiments were performed in hepatoma 7288CTC and inguinal fat pads in Buffalo rats during perfusion in situ. CLA isomers and trans FAs (0.03-0.4 mmol/L, in plasma) were added to the arterial blood, and FA uptake or release was measured by arterial minus venous difference. In hepatoma 7288CTC, the CLA isomers, t10,c12-CLA > (+/-)-9-HODE [13-(S)-hydroxyoctadecadienoic acid] > t9,t11-CLA, and the trans FAs, linolelaidic = vaccenic > elaidic, decreased cAMP content and inhibited FA uptake, 13(S)-HODE release, extracellular signal-regulated kinase p44/p42 phosphorylation, and [(3)H]thymidine incorporation. Other CLA isomers, c9,t11-CLA, 13-(S)-HODE, c9,c11-CLA, and c11,t13-CLA, had no effect. In inguinal fat pads, FA transport was inhibited by t10,c12-CLA = linolelaidic acid > trans vaccenic acid, whereas c9,t11-CLA had no effect. In both hepatoma 7288CTC and inguinal fat pad, addition of either pertussis toxin or 8-Br-cAMP to the arterial blood reversed the inhibitions of FA transport. These results support the idea that an inhibitory GPC FFAR reduces cAMP and controls FA transport by CLA isomers and trans FAs. Ligand activity is conferred by the presence of a trans double bond proximal to the carboxyl group.

Omega-3 (n-3) fatty acids are widely recognized as being important in regulating many inflammatory disorders in man. However, metabolism of the parent n-3 fatty acid a-linolenic acid (ALA, 18:3n-3) to the highly unsaturated bioactive fatty acids; eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA,, in the body is limited. The first product in the pathway leading to EPA/ DHA is the post-D6 desaturase metabolite stearidonic acid (SDA, 18:4n-3). The activity of the D6-desaturase enzyme is low in man and can be adversely influenced by several environmental factors including dietary fat. SDA has been shown, in several studies, to be rapidly and efficiently converted to EPA which is a probable factor in its bio-activity. The main source of EPA and DHA in diet is fish oil which, owing to over-fishing and its extensive use in aquaculture feed, is becoming a scarce resource. There clearly exists a need for a renewable source of a lipid containing the highly unsaturated n-3 fatty acids EPA, DHA or SDA. Although the highly unsaturated fatty acids (HUFA) have been commercially produced in micro-organisms neither EPA nor DHA has been shown to exist in any quantity in land-based plants. SDA is however found in several fungal and algal species and also in a small number of plant seed oils. Plants from the Boraginaceae family notably Echium species are particularly rich in SDA and Echium plantagineum has been grown commercially. Other plants from the Boraginaceae are being investigated and several have been identified that may offer benefits over Echium spp. Transgenic plants containing high levels of SDA have also been reported but engineering EPA or DHA into genetically modified higher plants is proving elusive. SDAcontaining lipids are of great interest in a number of areas such as fortified foods, dietary supplements, medicinal foods, pharmaceuticals and personal-care products.