Comparison of C18-, C20- and C22-unsaturated fatty acids in reducing fatty acid synthesis in isolated rat hepatocytes.

C18-, C20- and C22-unsaturated acids were tested for inhibition of fatty acid synthesis in hepatocytes isolated from essential fatty acid-deficient rats. Fatty acid synthesis was measured by incorporation of radioactivity from [1-14C-A1-acetate or 3H2O into fatty acids. C20-polyunsaturated fatty acids included arachidonic acid (20 : 4 (n-6)) and 4 other fatty acids formed from linoleic acid (18 : 2 (n-6)) or linolenic acid (18 : 3 (n-3)). These were (11,14)-icosadienoic acid (20 : 2 (n-6)), (8,11,14)-icosatrienoic acid (20 : 3 (n-6)), (11,14,17)-icosatrienoic acid (20 : 3 (n-3)) and (5,8,11,14,17)-icosapentaenoic acid (20 : 5 (n-3). All of these have essential fatty acid activity. The fatty acid (5,8,11)-icosatrienoic acid (20 : 3 (n-9)) was also tested. This fatty acid is formed from oleic acid (18 : 1 (n-9)) and is not an essential fatty acid or a prostaglandin precursor. C20-unsaturated fatty acids and (22 : 6 (n-3)) were as effective as stearic acid in inhibiting fatty acid synthesis and were more inhibitory than their precursor C18-unsaturated fatty acids. These results are evidence that C20-unsaturated fatty acids of the linoleic and linolenic acid series can act in short-term inhibition as well as in adaptive inhibition of fatty acid synthesis (Bloch, K. and Vance, D. (1977) Annu. Rev. Biochem. 46, 263--298). The effectiveness of (5,8,11)-icosatrienoic acid indicates that short-term inhibition by C20-unsaturated fatty acids is not limited to those fatty acids which have essential fatty acid activity.