Diet-induced obesity in rats can be produced by high-fat feeding. Comparing high-fat with low-fat feeding, the present study was designed to characterize the phases of development of obesity. In the dynamic phase, male rats were investigated at the age of 9-10 weeks after feeding the diets for 4-5 weeks. In the static phase, the animals at the age of 24-26 weeks were tested after 20-22 weeks of the nutritional regime. In this phase, the effects of switching high-fat to low-fat diet for 4 weeks were also examined. Fractionating lipid extracts by thin layer chromatography the concentrations of several lipids in epididymal adipose tissue, in serum, and in liver were determined. In liver, the enhancement of cholesteryl-ester (CE) concentration after high-fat feeding besides the accumulation of triglycerides (TG) is remarkable. Cell fractionation studies of the livers by differential ultracentrifugation showed the major part of the accumulated CE in the supernatant. In vitro incorporation of (1-14C)acetate and (2-14C)mevalonate into liver slices indicated that cholesterol synthesis in the liver of the obese rats was not increased. Although the offered fat diet with 0.1% of cholesterol can not be considered as high in cholesterol, the 2.5-fold higher amount of the high-fat diet in comparison with the low-fat diet (0.04% cholesterol) could be responsible for the enlargement of CE in the liver of the fat fed rats. This possibility was proved by measurement of the cholesterol absorption and transport to the liver after oral administration of (4-14C)cholesterol. Estimation of TG secretion rates of the liver using Triton WR 1339 pointed out higher rates in the obese rats in the dynamic phase. In the static phase, the rates were not different between both feeding groups, while fat restriction in the food produced a striking increase of TG secretion. It is assumed that only in the dynamic phase metabolism is able to compensate the liver TG accumulation by an enhanced transport to the adipose tissue. In the static phase this ability is diminished but not lost.

The influence of dietary fat on the fatty acid composition of liver and adipose tissue lipids was investigated after 4 and 19 weeks of high-fat feeding (50% fat) in comparison to low-fat feeding (3% fat), beginning in the sixth week of age. In rats fed the low-fat diet or an usual pellet diet the fatty pattern of liver triglycerides (TG) was equal to that of adipose tissue, while there were no similarities to the diet. In total liver lipids a constant fatty acid profile was observed, independently of the duration of feeding. High fat feeding results several changes in the fatty acid pattern of liver lipids. While after 4 weeks the fatty acids of liver TG more closely resembled the dietary fatty acids than those of adipose tissue, after 19 weeks of feeding the fatty acid composition of liver TG is comparable with that of adipose tissue. Not all rats fed the high fat diet rendered obese. It could be shown that in rats with higher lipid concentrations in the liver only the fatty acid pattern of liver phospholipids has been altered, while the composition of TG, which are the lipids primarily increased, was not changed.

The influence of thyroxine, estradiol and testosterone on the triacylglycerol (TG) secretion rate out of the liver into the blood as well as on concentrations of FFA, triglycerides, and glucose in serum was determined. All of these experiments were carried out under different nutritional conditions (non-fasting, and 10 or 16 h fasting, respectively). Accordingly the results after hormone application were compared with three groups of controls. Within these control groups increasing time of fasting caused exclusively an enhancement of FFA concentrations, while the TG secretion rate and other parameters were not influenced. Concerning all hormones effects on several lipid parameters have been observed. In particular, a decrease of FFA concentrations in comparison with controls after 16 h fasting was evident. In these cases, the TG secretion rate and TG concentration in serum were simultaneously lowered. Both alterations may be a consequence of a diminished mobilization of FFA in adipose tissue. Increases of FFA concentrations in serum after hormone application, compared with the corresponding controls, only occurred after administration of thyroxine and testosterone, while changes of the TG secretion rate and the TG concentration in serum were scarcely observed. Final remarks about the actual influence of hormones on the investigated parameters, especially TG secretion rate were drawn including results of a previous paper, where catecholamines, insulin, and prednisolone had been tested under the same conditions.

The authors investigated in rats with dietarily-induced obesity certain biochemical parameters of the blood plasma as well as body and organ weights during the dynamic and the static phase of obesity development. They determined total cholesterol, total protein, albumin, creatinine, urea nitrogen and transaminases. After 4-5 weeks, the animals on a high-diet (50% of fat) had body weights which were, on an average, by 90% higher than those of the control animals. This difference persisted during the static phase. In the animals on a high-fat diet, body length was greater. The high-fat diet (which contains a great proportion of sunflower oil) leads to a decrease of the plasma cholesterol level in obese rats. The plasma-protein bodies, creatinine and urea nitrogen values as well as those for transaminases permit, as parameters for function and damage, to draw conclusions as to kidney and liver damages in the animals on high-fat diet. There were no differences in plasma protein between the control and experimental animals. On the contrary, obese rats showed in some cases high creatinine concentrations during the dynamic phase. Differences in urea nitrogen were not observed between the two groups of animals. Increases in alanine aminotransferase were found in the animals on high-fat diet as a manifestation of fatty degeneration of the liver. A synopsis of weight curves, biochemical parameters and histological findings permits the conclusion that, besides of dietarily-induced metabolic alterations, no additional organic lesions occurred during the present animal experiment on dietarily-induced obesity.

The influence of epinephrine, norepinephrine, insulin, and prednisolone on the triacylglycerol (TG) secretion rate of rat liver was determined in vivo under different nutritional conditions (non-fasting, 10 and 16 h fasting, respectively). It was possible to estimate the triacylglycerol secretion rate by the Triton method without regard to fasting intervals. The subcutaneous administration of hormones was followed in all cases by changes of lipid parameters. Variations of secretion rate were found only by applications of norepinephrine, insulin, and prednisolone. Frequently, but not always, a change of free fatty acid (FFA) concentration in serum, that means a change of FFA mobilization in adipose tissue, was accompanied by an alteration of the TG secretion rate and in some cases by a change of TG concentration in serum in the same direction. We suggest that under these conditions the hormonal effect on TG secretion is realized by influence on the mobilization of FFA in adipose tissue. If the enhancement of FFA in serum is not followed by an increase of TG secretion, the elevated FFA influx into the liver is possibly used for oxidation or synthesis of phospholipids too. The role of nutritional factors was especially seen in 16 h fasting animals in which no rise of TG secretion rate was observed in spite of high FFA levels. In some cases reduced serum TG concentrations were observed without preceeding decreases of TG secretion rate out of the liver. Probably this effect is caused by increased clearance of serum TG.