Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism.
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.
Yeang
Calvin
C
Department of Cell Biology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY, USA.
Qin
Shucun
S
Chen
Kailian
K
Wang
David Q-H
DQ
Jiang
Xian-Cheng
XC
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D004032:Diet; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D010743:Phospholipids / Q000097:blood*
D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C510091:phospholipid transfer protein, mouse; D002784:Cholesterol