DIETARY SUPPLEMENTATION OF VERY LONG-CHAIN N-3 FATTY-ACIDS DECREASES WHOLE-BODY LIPID UTILIZATION IN THE RAT

Rats were fed lard or n-3 fatty acid-supplemented diets ad libitum to study whole body oxidation of lipid and carbohydrate. One group of mal e rats was fed 21% fat (by weight) containing 19.5% lard and sufficien t amounts of essential fatty acids (1.5%). Another group of rats had 6 .5% of the lard replaced by ethyl esters of eicosapentaenoic acid (EPA ) and docoshexaenoic acid (DHA). The rats were fed these diets for 6-8 weeks. Body weight gain was similar for the two groups and absorption of fat was complete in animals fed both types of fatty acids. Indirec t calorimetric measurements, after 3-5 weeks on these diets, by contin uous registration Of O2 consumption and CO2 formation showed no differ ence in mean energy expenditure during the experimental period. Howeve r, the mean respiratory quotient (RQ) was significantly increased for animals fed the n-3 fatty acid-supplemented diet. This was noted both under fasting conditions and after receiving a test meal of similar fa tty acid composition for both feeding groups. Thus, mean substrate uti lization demonstrated reduced oxidation of fat and increased oxidation of carbohydrate, during fasting as well as fed periods for the n-3 fa tty acid group as compared to the lard group. After an additional 2-3 weeks, blood plasma, liver, and muscle samples were collected, and adi pocytes and hepatocytes were isolated. Reduced postprandial plasma con centrations of triacylglycerol, phospholipids, unesterified fatty acid s, and glycerol were promoted by the n-3 fatty acid diet as compared t o lard. Plasma concentration of glucose was slightly increased, and li ver and muscle content of glycogen were decreased in the n-3 fatty aci d-fed rats. Experiments with isolated adipocytes showed decreased basa l lipolysis after feeding n-3 fatty acids for 6-8 weeks for suspended epididymal adipocytes, whereas stimulated lipolysis by isoproterenol ( 0.1 muM) was higher in both epididymal and mesenteric adipocytes from rats fed n-3 fatty acids as compared to animals fed lard. In addition, epididymal adipocytes from rats fed n-3 fatty acids were significantl y smaller than cells from animals fed lard. Hepatic peroxisomal fatty acid oxidation was significantly higher for n-3 fatty acid-supplemente d animals, but total fatty acid oxidation was similar in both dietary groups. The hepatic content of triacylglycerol and phospholipids was s imilar for both diets. These results demonstrate that n-3 fatty acid r eplacement of a high-fat diet containing mostly saturates and monoenes for several weeks promotes reduced use of fat as energy source. This may be explained by decreased plasma concentration of unesterified fat ty acids. Along with reduced plasma concentration of glycerol, our dat a could be interpreted as reduced lipolysis. These changes in plasma l ipids may promote reduced triacylglycerol storage in certain adipose t issues, as well as decreased fatty acid availability to the liver for synthesis and secretion of VLDL and increased carbohydrate utilization .