Octanoate reduces very low-density lipoprotein secretion by decreasing the synthesis of apolipoprotein B in primary cultures of chicken hepatocytes.
Fatty acids of varying lengths and saturation differentially affect plasma apolipoprotein B (apoB) levels. To identify the mechanisms underlying the effect of octanoate on very low-density lipoprotein (VLDL) secretion, chicken primary hepatocytes were incubated with either fatty acid-bovine serum albumin (BSA) complexes or BSA alone. Addition of octanoate to culture medium significantly reduced VLDL-triacylglycerol (TG), VLDL-cholesterol and apoB secretion from hepatocytes compared to both control cultures with BSA only and palmitate treatments, but did not modulate intracellular TG accumulation. However, no differences in cellular microsomal triglyceride transfer protein levels were observed in the cultures with saturated fatty acid. In pulse-chase studies, octanoate treatment resulted in reduced apoB-100 synthesis, in agreement with its promotion of secretion. This characteristic effect of octanoate was confirmed by addition of a protease inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN), to hepatocyte cultures. Analysis showed that the level of apoB mRNA was lower in cultures supplemented with octanoate than in the control cultures, but no significant changes were observed in the levels of apolipoprotein A-I, fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase mRNA as a result of octanoate treatment. Time-course studies indicate that a 50% reduction in apoB mRNA levels requires 12 h of incubation with octanoate. We conclude that octanoate reduced VLDL secretion by the specific down-regulation of apoB gene expression and impairment of subsequent synthesis of apoB, not by the modulation of intracellular apoB degradation, which is known to be a major regulatory target of VLDL secretion of other fatty acids.
Tachibana
Shizuko
S
Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 981-8555, Japan.
Sato
Kan
K
Cho
Yoshitake
Y
Chiba
Tomoyuki
T
Schneider
Wolfgang J
WJ
Akiba
Yukio
Y
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D002210:Caprylates / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D015243:Cholesterol, VLDL / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D022781:Hepatocytes / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D007976:Leupeptins / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002210:Caprylates; D002352:Carrier Proteins; D015243:Cholesterol, VLDL; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; C030106:very low density lipoprotein triglyceride; C063261:acetylleucyl-leucyl-norleucinal; D019308:Palmitic Acid; D006903:Hydroxymethylglutaryl CoA Reductases; D064429:Fatty Acid Synthases; C031492:octanoic acid