Abstract
A high saturated fat diet induces free cholesterol and phospholipid accumulation in the plasma of phospholipid transfer protein (Pltp)-deficient mice. In this study, we examined the atherogenic consequence of this phenomenon and investigated the possible mechanism(s). Pltp KO/Apoe KO mice that were fed a coconut oil-enriched high-fat diet (COD) for 7 weeks had higher plasma free cholesterol (149%), phospholipids (15%), and sphingomyelin (54%) than Apoe KO controls. In contrast to chow-fed animals, COD-fed Pltp KO/Apoe KO mice had the same atherosclerotic lesion size as that of Apoe KO mice. Similar to Pltp KO mice, plasma from COD-fed Pltp KO/Apoe KO mice contained VLDL/LDL-sized lamellar particles. Bile measurement indicated that COD-fed Pltp KO mice have 33% less hepatic cholesterol output than controls. In conclusion, COD-fed, Pltp-deficient mice are no longer protected from atherosclerosis and have impaired biliary lipid secretion, which is associated with free cholesterol and phospholipid accumulation.
Highlights
A high saturated fat diet induces free cholesterol and phospholipid accumulation in the plasma of phospholipid transfer protein (Pltp)-deficient mice
We examined the effect of coconut oil-enriched high-fat diet (COD) on plasma lipid levels in Pltp KO/Apoe KO and Apoe KO mice, as we observed that feeding COD significantly increased plasma free cholesterol levels in all Pltp-deficient mice [2, 8]
Biliary phospholipid output was diminished by 25% in Pltp KO mice (Fig. 8C). These results indicate that in the COD-fed state, Pltp deficiency could reduce hepatic secretion of biliary cholesterol, which could contribute to the accumulation of plasma free cholesterol in these mice
Summary
A high saturated fat diet induces free cholesterol and phospholipid accumulation in the plasma of phospholipid transfer protein (Pltp)-deficient mice. Pltp KO/Apoe KO mice that were fed a coconut oil-enriched high-fat diet (COD) for 7 weeks had higher plasma free cholesterol (149%), phospholipids (15%), and sphingomyelin (54%) than Apoe KO controls. PLTP deficiency in mice results in a large decrease in plasma lipid levels, including total cholesterol, cholesteryl ester, and phospholipids, when the mice are fed a chow diet [2, 8] or Western-type diet consisting of 20% milk fat plus 0.15% cholesterol [8]. When fed a high-fat diet consisting of 20% saturated fat from coconut oil and 0.15% cholesterol (COD), Pltp knockout (KO) mice accumulate more free cholesterol and phospholipids than wildtype (WT) controls [8]. Pltp KO/Apoe KO mice have significantly less atherosclerosis than Apoe KO controls [4]
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