Effect of a high-fat diet on rat very low density lipoprotein secretion.

1. Very low density lipoprotein (VLDL) secretion rates were studied on rats adapted to a high-fat diet (71% calories as lard) for 3-4 weeks, compared to control (starch-fed) rats. 2. Experiments were performed at 14.00 h, at which time all animals had the same circulating free fatty acids. Fat-fed rats presented an apparent liver stealosis, a high post-Triton chylomicron secretion, but a 40% decreased VLDL secretion. 3. Injection of [1-14C]palmitic acid showed that the tracer was incorporated less in liver triacylglycerols of the fat-fed rats, presumably because of an enhanced ketogenesis. Secretion of labelled VLDL-triacylglycerols in 1 h was diminished 5-fold, even after a correction for the lower hepatic esterification. 4. Two complementary experiments were carried out, with the following results: at 08.00 h, when serum free fatty acid concentrations were comparable in both groups of rats [5,10], post-Triton VLDL secretion was diminished by 45% in the fat-fed rats; at 20.00 h, the fat-fed rats had significantly elevated plasma free fatty acids [5,10], but their VLDL secretion was the same as in control rats. 5. So it appears that in fat-fed rats circulating free fatty acids do not stimulate VLDL secretion as expected. It is suggested that the decreased VLDL secretion with the high-fat diet may result from inhibition of hepatic lipogenesis.