Effect of n-3 fatty acids on serum lipid levels and hepatic fatty acid metabolism in BALB/c.KOR-Apoeshl mice deficient in apolipoprotein E expression.
N-3 fatty acids exert a potent serum lipid-lowering effect in rodents mainly by affecting hepatic fatty acid oxidation and synthesis. However, it has been observed that fish oil and docosahexaenoic acid ethyl ester do not lower serum lipid levels in apolipoprotein E (apoE)-knockout (Apoetm1Unc) mice generated by gene targeting. To test the hypothesis that apoE expression is required for n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism, we examined the effect of fish oil and n-3 fatty acid ethyl esters on the activity and gene expression of hepatic enzymes involved in fatty acid oxidation and synthesis using an alternative apoE-deficient mouse model with the BALB/c genetic background (BALB/c.KOR-Apoeshl). ApoE-deficient mice were fed diets containing 9.4% palm oil, fish oil, or 5.4% palm oil and 1% EPA plus 3% DHA ethyl esters for 15 days. In contrast to the reported data on apoE-knockout mice, fish oil and n-3 fatty acid ethyl esters greatly decreased serum triacylglycerol, cholesterol, and phospholipid levels in the Apoeshl mice. The decreases were greater with fish oil than with ethyl esters. The alterations by dietary n-3 fatty acids of serum lipid levels were accompanied by parallel changes in the activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation and synthesis. The reason for the discrepancy between the results of the current study and previous studies is unknown. However, our study at least indicates that a lack of apoE expression does not necessarily accompany deficits in the n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism.
Ide
Takashi
T
Laboratory of Nutritional Biochemistry, National Food Research Institute, 2-1-12 Kannondai, Tsukuba 305-8642, Japan. idetaka@nfri.affrc.go.jp
Takahashi
Yoko
Y
Kushiro
Masayo
M
Tachibana
Masayoshi
M
Matsushima
Yoshibumi
Y
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics*; D015152:Blotting, Northern; D001835:Body Weight; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D001057:Apolipoproteins E; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008055:Lipids; D012333:RNA, Messenger; D012313:RNA; D010100:Oxygen