Pramod Khosla

Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Rabbits fed low-fat, cholesterol-free, semi-purified diets containing casein become hypercholesterolemic, whereas rabbits whose diets contain soy protein, maintain low levels of plasma cholesterol. Experiments were carried out in attempts to further understand this phenomenon.;Time course studies showed that on being transferred from a Chow diet, plasma cholesterol levels increased markedly in casein-fed rabbits. The increase was particularly prominent in the LDL fraction, in which the cholesterol and protein increased appreciably in the first two weeks. Subsequently LDL cholesterol increased more slowly, and LDL protein levels held steady. In contrast rabbits transferred to soy protein maintained low levels of plasma cholesterol throughout the study.;To ascertain if the elevation in LDL in casein fed rabbits resulted from increased production and/or decreased catabolism of these particles, dual-labeled kinetic studies were carried out. These studies showed that the increased LDL pool resulted principally from a decreased efficiency of removal. In addition, the expanded LDL pool was the result of increased LDL production via VLDL-independent pathways.;Further studies showed that the diminished catabolism of LDL in casein-fed rabbits was due to impaired receptor-dependent catabolism and not to any functional abnormalities in the LDL particles themselves. Additional studies showed that impaired receptor-dependent catabolism of LDL in casein-fed rabbits, could be detected within 5 days of casein-feeding and, before, any detectable increase in plasma cholesterol.;Experiments, conducted to see if the impaired receptor-mediated catabolism in casein-fed rabbits resulted from differences in the digestibility of the dietary proteins, in vivo, collectively suggested that there was no difference in digestibility.;Casein-fed rabbits had significantly lower post-prandial levels of Cholecystokinin (CCK). Exogenous injections of CCK into casein-fed rabbits tended to slow the development of hypercholesterolemia.;These studies show that the elevated LDL pool in casein-fed rabbits is the result of impaired receptor-dependent LDL catabolism. This is attributed to the protein component of the diet since it did not occur with soy protein diets. The change may be hormonally mediated.



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