Elevated hepatic apolipoprotein A-I transcription is associated with diet-induced hyperalphalipoproteinemia in rabbits.
Past studies have shown that a high saturated fatty acid diet containing coconut oil elevates plasma HDL cholesterol and apolipoprotein A-I (apoA-1) in rabbits through a mechanism involving increased synthesis. We have extended those studies by investigating expression of the hepatic apolipoprotein A-I gene and other lipid related genes in that model. Rabbits fed a diet containing 14% coconut oil for 4 weeks showed HDL-C elevations of 170% to 250% over chow-fed controls with peak differences occurring at 1 week. Plasma apoA-I levels were also increased over this time frame (160% to 180%) reflecting the HDL-C changes. After 4 weeks, there were no differences in plasma VLDL-C or LDL-C levels in chow versus coconut oil-fed rabbits. Hepatic levels of apoA-I mRNA in coconut oil-fed animals were elevated 150% after 4 weeks compared to chow-fed controls; hepatic mRNA levels for ten other genes either decreased slightly (apoB, LCAT, hepatic lipase, albumin, ACAT, and HMG CoA reductase) or were unchanged (CETP, apoE, LDL-receptor, and acyl CoA oxidase). Nuclear run-on transcription assays revealed that coconut oil feeding for 4 weeks caused a 220% increase in hepatic apoA-I transcription rate compared to controls; no change was observed for CETP and apoE. Treatment of cultured rabbit liver cells with various saturated fatty acids and sera from chow-fed and coconut oil-fed rabbits did not alter apoA-I mRNA levels as observed in vivo. These data demonstrate that coconut oil elevates plasma HDL-C and apoA-I by increasing hepatic apoA-I transcription while expression of other genes involved in lipid metabolism are reduced or unchanged in response to coconut oil feeding.
Schwab
D A
DA
Department of Molecular Biology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert, Ann Arbor, MI 48105, USA.
Rea
T J
TJ
Hanselman
J C
JC
Bisgaier
C L
CL
Krause
B R
BR
Pape
M E
ME
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000074263:Coconut Oil; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006951:Hyperlipoproteinemias / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000096:biosynthesis; D008075:Lipoproteins, HDL / Q000097:blood*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010938:Plant Oils / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
D016632:Apolipoprotein A-I; D004041:Dietary Fats; D005227:Fatty Acids; D020738:Leptin; D008075:Lipoproteins, HDL; D010938:Plant Oils; D012333:RNA, Messenger; D004247:DNA; D000074263:Coconut Oil