Journal of Lipid Research, Vol 34, 1299-1309, Copyright © 1993 by Lipid Research, Inc.

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Dietary supplementation of very long-chain n-3 fatty acids decreases whole body lipid utilization in the rat

AC Rustan, BE Hustvedt and CA Drevon
Department of Pharmacology, University of Oslo, Norway.

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 male rats was fed 21% fat (by weight) containing 19.5% lard and sufficient 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 docosahexaenoic 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. Indirect calorimetric measurements, after 3-5 weeks on these diets, by continuous registration of O2 consumption and CO2 formation showed no difference in mean energy expenditure during the experimental period. However, 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 fatty acid composition for both feeding groups. Thus, mean substrate utilization demonstrated reduced oxidation of fat and increased oxidation of carbohydrate, during fasting as well as fed periods for the n-3 fatty acid group as compared to the lard group. After an additional 2-3 weeks, blood plasma, liver, and muscle samples were collected, and adipocytes and hepatocytes were isolated. Reduced postprandial plasma concentrations of triacylglycerol, phospholipids, unesterified fatty acids, and glycerol were promoted by the n-3 fatty acid diet as compared to lard. Plasma concentration of glucose was slightly increased, and liver and muscle content of glycogen were decreased in the n-3 fatty acid-fed rats. Experiments with isolated adipocytes showed decreased basal lipolysis after feeding n-3 fatty acids for 6-8 weeks for suspended epididymal adipocytes, whereas stimulated lipolysis by isoproterenol (0.1 microM) 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 significantly smaller than cells from animals fed lard. Hepatic peroxisomal fatty acid oxidation was significantly higher for n-3 fatty acid-supplemented animals, but total fatty acid oxidation was similar in both dietary groups. The hepatic content of triacylglycerol and phospholipids was similar for both diets. These results demonstrate that n-3 fatty acid replacement 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 fatty acids.(ABSTRACT TRUNCATED AT 400 WORDS)
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