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Control of Hep G2-cell triacylglycerol and apolipoprotein B synthesis and secretion by polyunsaturated non-esterified fatty acids and insulin.

ABSTRACT: Non-esterified fatty acids (NEFAs) and insulin are important factors in the control of lipoprotein secretion, but the mechanism of action is unclear. The present study was undertaken to determine whether insulin and NEFAs modulated hepatic secretion of triacylglycerol and apolipoprotein B (apo-B) by regulation of hepatic intracellular apo-B content. The experiments were performed with the human hepatoblastoma cell line Hep G2, for periods of up to 72 h in the presence and absence of NEFAs and insulin. Higher concentrations of eicosapentanoate (EPA) sustained for 72 h decreased cellular protein content (at 250 microM) or caused cell death (at 750 microM), and this effect was not observed with the other NEFAs studied, whereas 75 microM-EPA did not affect cell viability. Compared with the absence of NEFA, 75 microM-EPA did not alter the intracellular triacylglycerol content, but decreased the intracellular content of apo-B by 47% (P < 0.01) and decreased secreted triacylglycerol and secreted apo-B by 13% (P < 0.05) and 21% (P < 0.01) respectively, after 72 h. However 250 microM-oleate increased the intracellular triacylglycerol by 36% (P < 0.01), intracellular apo-B by 22% (P < 0.05) and secreted triacylglycerol and apo-B by 20-30% (P < 0.05-0.01). Insulin decreased secreted triacylglycerol and apo-B in the presence of each NEFA studied by 20-30%. There was no correlation between the changes in intracellular triacylglycerol and the rate of secretion. However, when the secreted triacylglycerol or apo-B was plotted against intracellular apo-B content a significant correlation was observed (r = 0.89, P < 0.001 for both analyses). Apo-B mRNA levels did not change after 72 h incubation with oleate or EPA. These results demonstrate that EPA can be toxic to hepatocytes and that NEFAs and insulin control secretion of triacylglycerol and apo-B by regulation of the intracellular apo-B concentration, thus controlling assembly of apo-B with triacylglycerol to form lipoproteins.

SUBMITTER: Byrne CD

PROVIDER: S-EPMC1132085 | biostudies-other | 1992 Nov

REPOSITORIES: biostudies-other

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Project description:Background:The substitution of omega (?)-6 (n-6) polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) is advocated in cardiovascular disease prevention. The impact of this substitution on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains unknown. Objective:In men with dyslipidemia and IR, we evaluated the impact of substituting ?-6 PUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo) B-containing lipoproteins and on the intestinal expression of key genes involved in lipoprotein metabolism. Design:Dyslipidemic and IR men (n = 36) were recruited for this double-blind, randomized, crossover, controlled trial. Subjects consumed, in a random order, a fully controlled diet rich in SFAs (SFAs: 13.4% of energy; ?-6 PUFAs: 4.0%) and a fully controlled diet rich in ?-6 PUFAs (SFAs: 6.0%; ?-6 PUFAs: 11.3%) for periods of 4 wk, separated by a 4-wk washout period. At the end of each diet, the in vivo kinetics of apoB-containing lipoproteins were measured and the intestinal expression of key genes involved in lipoprotein metabolism was quantified in duodenal biopsies taken from each participant. Results:The substitution of ?-6 PUFAs for SFAs had no impact on TRL apoB-48 fractional catabolic rate (? = -3.8%, P = 0.7) and production rate (? = +1.2%, P = 0.9), although it downregulated the intestinal expression of the microsomal triglyceride transfer protein (? = -18.4%, P = 0.006) and apoB (? = -16.6%, P = 0.005). The substitution of ?-6 PUFAs for SFAs decreased the LDL apoB-100 pool size (? = -7.8%; P = 0.005). This difference was attributed to a reduction in the LDL apoB-100 production rate after the substitution of ?-6 PUFAs for SFAs (? = -10.0%; P = 0.003). Conclusions:This study demonstrates that the substitution of dietary ?-6 PUFAs for SFAs decreases the production and number of LDL particles in men with dyslipidemia and IR. This trial was registered at clinicaltrials.gov as NCT01934543.

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Control of Hep G2-cell triacylglycerol and apolipoprotein B synthesis and secretion by polyunsaturated non-esterified fatty acids and insulin.

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