We studied ketonemia induced in rats by a single oral load of medium-chain triglycerides (MCT) (C8:0 50.5%, C10:0 48.0%, C12:0 1.0%). Medium-chain fatty acids, rather than being incorporated into the lipids synthesized by the liver, are oxidized there, with high production of ketone bodies. Severe and long-lasting hyperketonemia developed rapidly. With increased MCT loads, ketonemia also increased, although not linearly. The level of the hyperketonemia seemed equal in the two sexes. Ingestion of MCT by fasting rats caused an additional rise in ketonemia. Long-chain triglycerides were not ketogenic, since their constituent fatty acids are incorporated into lipids and are thus less subject to oxidation. Lipids induce less severe ketonemia in genetically obese rats than in normal-weight rats.

Changes in a number of morphological and biochemical parameters were observed in genetically obese Zucker rats and in lean controls between 3 and 58 weeks of age. By 3 weeks, the genetically obese rats had higher proportional (wt/100 g body wt) and absolute amounts of adipose tissue, hyperlipemia affecting all the lipid fractions, and hyperproteinemia compared to lean controls. Obesity, hepatomegaly, high concentrations of hepatic lipids and hyperinsulinemia did not appear until the fifth week. In obese animals, liver lipid concentration reached a maximum at 17 weeks of age and then declined. During this time, the triacylglycerol concentration in the serum remained stable, whereas the cholesterol and phospholipid concentrations continued to increase. The glycogen concentration in obese animals increased, both absolutely and compared to lean controls, between the 12th and 43rd weeks of age. From weaning, the Zucker rats, compared to lean controls, exhibited characteristics of obesity (accumulation of adipose tissue, hyperlipemia and hyperproteinemia), which persisted to the age of 58 weeks.

A study of the various biological parameters of the blood in the genetically obese Zucker rat, the nonobese Zucker rat, and the Wistar rat has revealed great similarity between the two latter types of animals. On the other hand, in genetically obese Zucker rats as compared with the nonobese ones, (1) the blood mass per unit of weight was lower; (2) the level of nitrogenous degradation compounds was the same; (3) the lipase activity was lower; (4) the levels of substances for which liver plays a crucial role--all lipid and protein fractions, glucose, and the enzyme GPT--were higher; (5) the levels of Ca, Zn, Fe, Cu and Pi were high; (6) the blood and bone-marrow cells were unremarkable.

To test whether the property of medium-chain fatty acids (which have 6-12 carbon atoms) being incorporated only in small amounts into the various tissues of a living organism could be exploited to treat obesity, genetically obese Zucker rats and their lean littermates were fed a diet containing 20% medium-chain triacylglycerols (MCT) or long-chain triacylglycerols (LCT) for 10 weeks. MCT, as compared with LCT, had the following effects: 1) MCT did not diminish weight gain in either the nonobese or the obese rats; 2) they increased ketogenesis more in the former than in the latter; 3) they increased the concentration of triacylglycerols in the liver of the obese rats but not of the lean ones; 4) they decreased the concentration of cholesterol in the liver of the lean but not of the obese rats, and 5) they did not particularly affect the concentration of proteins, glucose and insulin in the blood. We therefore conclude that the influence of the genotype is much more important in the establishment of the biochemical characteristics of rats than is the nature of the fatty acids ingested. Replacing LCT in the diet with MCT did not correct any of the major metabolic disorders in obese rats and therefore cannot unaided constitute a solution to the problem of genetic obesity.

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