ESSENTIAL FATTY-ACID METABOLISM IN THE FELINE - RELATIONSHIP BETWEEN LIVER AND BRAIN PRODUCTION OF LONG-CHAIN POLYUNSATURATED FATTY-ACIDS

A comparison was made between the liver and brain conversion of linoleic acid, 18:2n-6, and linolenic acid, 18:3n-3, to long chain polyunsaturated fatty acids in domestic felines. This report demonstrates that 6-desaturase activity does exist in the feline. The liver produced deuterium-labeled polyunsaturated fatty acids up to 22:4n-6 and 22:5n-3. The brain was found to accumulate the deuterium-labeled polyunsaturated fatty acids, 22:5n-6, 22:6n-3, 24:4n-6, 24:5n-6, 24:5n-3, and 24:6n-3. Adult felines were provided a diet consisting of either 10% fat (hydrogenated coconut oil-corn oil 9:1) containing no 20- or 22-carbon n-6 or n-3 fatty acids or a chow diet with meat and meat by-products that contained these long chain polyunsaturated fatty acids for a 6-month period. During this time, the in vivo production of long chain polyunsaturated fatty acids was evaluated in these animals. The cats were given oral doses of both [17,17,18,18,18-H-2]18:3n-3 and [9,10,12,13-H-2]18:2n-6 and the deuterium-labeled fatty acid metabolites were measured in the blood, liver, and brain using a highly sensitive and specific gas chromatography-mass spectrometry technique. Contrary to previous claims, 6-desaturase activity was shown to exist in the feline. The evidence for this was the detection of [9,10,12,13-H-2] 18:3n-6 which was converted from [9,10,12,13-H-2]18:2n-6 and observed in the plasma. For the first time, direct evidence for the metabolism of n-3 fatty acids in cats was obtained by the detection of deuterium-labeled metabolites including the polyunsaturated fatty acid, 22:5n-3, in the plasma, following an oral dose of deuterium-labeled 18:3n-3. The more highly unsaturated deuterium-labeled 22- and 24-carbon fatty acids including: 22:6n-3, 24:5n-3, 24:6n-3, 22:5n-6, 24:4n-6, and 24:5n-6 accumulated in the nervous system. These deuterium-labeled fatty acids were not detected in either the liver or plasma. As the liver was found to produce and export into the blood the deuterium-labeled 22:5n-3 and 22:4n-6, it is suggested that these intermediates are then transported to the brain and retina where they are converted to 22:6n-3 and 22:5n-6, respectively. This route for the accretion of 22:6n-3 in the nervous system has not been previously proposed. In the feline, it appears that both the liver and the brain are involved in biosynthesizing long-chain polyunsaturated fatty acids when no preformed 20- and 22-carbon essential fatty acids are present in the diet.