Effects of dietary fats and cholesterol on liver lipid content and hepatic apolipoprotein A-I, B, and E and LDL receptor mRNA levels in cebus monkeys.
The effects of the long-term administration of the dietary fats coconut oil and corn oil at 31% of calories with or without 0.1% (wt/wt) dietary cholesterol on plasma lipoproteins, apolipoproteins (apo), hepatic lipid content, and hepatic apoA-I, apoB, apoE, and low density lipoprotein (LDL) receptor mRNA abundance were examined in 27 cebus monkeys. Relative to the corn oil-fed animals, no significant differences were noted in any of the parameters of the corn oil plus cholesterol-fed group. In animals fed coconut oil without cholesterol, significantly higher (P less than 0.05) plasma total cholesterol (145%), very low density lipoprotein (VLDL) + LDL (201%) and high density lipoprotein (HDL) (123%) cholesterol, apoA-I (103%), apoB (61%), and liver cholesteryl ester (263%) and triglyceride (325%) levels were noted, with no significant differences in mRNA levels relative to the corn oil only group. In animals fed coconut oil plus cholesterol, all plasma parameters were significantly higher (P less than 0.05), as were hepatic triglyceride (563%) and liver apoA-I (123%) and apoB (87%) mRNA levels relative to the corn oil only group, while hepatic LDL receptor mRNA (-29%) levels were significantly lower (P less than 0.05). Correlation coefficient analyses performed on pooled data demonstrated that liver triglyceride content was positively associated (P less than 0.05) with liver apoA-I and apoB mRNA levels and negatively associated (P less than 0.01) with hepatic LDL receptor mRNA levels. Liver free and esterified cholesterol levels were positively correlated (P less than 0.05) with liver apoE mRNA levels and negatively correlated (P less than 0.025) with liver LDL receptor mRNA levels. Interestingly, while a significant correlation (P less than 0.01) was noted between hepatic apoA-I mRNA abundance and plasma apoA-I levels, no such relationship was observed between liver apoB mRNA and plasma apoB levels, suggesting that the hepatic mRNA of apoA-I, but not that of apoB, is a major determinant of the circulating levels of the respective apolipoprotein. Our data indicate that a diet high in saturated fat and cholesterol may increase the accumulation of triglyceride and cholesterol in the liver, each resulting in the suppression of hepatic LDL receptor mRNA levels. We hypothesize that such elevations in hepatic lipid content differentially alter hepatic apoprotein mRNA levels, with triglyceride increasing hepatic mRNA concentrations for apoA-I and B and cholesterol elevating hepatic apoE mRNA abundance.
Hennessy
L K
LK
USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Osada
J
J
Ordovas
J M
JM
Nicolosi
R J
RJ
Stucchi
A F
AF
Brousseau
M E
ME
Schaefer
E J
EJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000235:genetics; D001053:Apolipoproteins / Q000187:drug effects* / Q000235:genetics; D001055:Apolipoproteins B / Q000187:drug effects / Q000235:genetics; D001057:Apolipoproteins E / Q000187:drug effects / Q000235:genetics; D002428:Cebus; D002784:Cholesterol / Q000097:blood / Q000494:pharmacology*; D000074263:Coconut Oil; D003314:Corn Oil / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010938:Plant Oils / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D011973:Receptors, LDL / Q000187:drug effects* / Q000235:genetics; D018110:Receptors, Lipoprotein
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D004041:Dietary Fats; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010938:Plant Oils; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C064018:apolipoprotein A-I A-II receptor; D003314:Corn Oil; D002784:Cholesterol; D000074263:Coconut Oil