Effects of oleic acid on the biosynthesis of lipoprotein apoproteins and distribution into the very-low-density lipoprotein by the isolated perfused rat liver

Salam, W H; Wilcox, Henry G.; Heimberg, Murray

doi:10.1042/bj2510809

Cited by 59 publications

(32 citation statements)

References 48 publications

(34 reference statements)

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“…For example, while in HepG2 cells oleic acid stimulation of lipogenesis augments apoB secretion (8,10,20,36,37), there is no effect in primary rat hepatocytes (38,39). Additional studies show that oleic acid increases apoB secretion when infused into livers from fasted rats but not when infused into livers from fed rats (40). A rate-limiting or paused translocation step (27,28) may act in concert with MTP and the availability of specific lipids to provide the opportunity to efficiently package lipid into lipoproteins for export from the liver and intestine.…”

Section: Discussionmentioning

confidence: 99%

In HepG2 Cells, Translocation, Not Degradation, Determines the Fate of the de Novo Synthesized Apolipoprotein B

Bonnardel¹,

Davis²

1995

Journal of Biological Chemistry

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Previous studies show that translocation and degradation of apolipoprotein B (apoB), two processes occurring on or within the endoplasmic reticulum, determine how much de novo synthesized apoB is secreted. We determined which of these processes regulates the intracellular fate of apoB by examining whether degradation determines how much apoB is translocated or if translocation determines how much apoB is degraded. 35 S]methionine-labeled proteins), its effect on apoB was specific. Pulsechase studies showed that ALLN dramatically reduced the first-order rate of removal of [ 35 S]methionine-labeled apoB from the cell but did not effect its rate of secretion. The finding that ALLN caused the intracellular accumulation of incompletely translated chains of apoB suggests that at least some of the degradation occurs at the ribosomal level. Moreover, 85% of the apoB that accumulated in isolated microsomes in response to ALLN was accessible to exogenous trypsin, indicating this pool of apoB was incompletely translocated. The combined data suggest that translocation, not degradation, determines the intracellular fate of de novo synthesized apoB. apoB 1 is the major structural protein responsible for the assembly of triglyceride-rich lipoproteins by the intestine and liver (1-3). After secretion into blood plasma by the liver, VLDL triglycerides are rapidly hydrolyzed into free fatty acids, which are taken up by peripheral tissues where they are utilized for energy and anabolic purposes. The remaining VLDL remnants, containing apoB100, are then either removed by the liver or converted into LDL, a major risk factor for atherosclerosis (reviewed in Ref. 4). Because of the importance of hepatic secretion of VLDL apoB in determining blood levels of LDL, a major goal of our research has been directed toward identifying the regulatory factors and processes.We have made two observations, both of which have shown unusual characteristics governing the hepatic secretion of apoB: 1) a large amount of de novo synthesized apoB is not secreted but is degraded intracellularly (5) and 2) the translocation of apoB across the endoplasmic reticulum is unusually inefficient (6). These results led us to hypothesize that as a result of incomplete translocation, apoB is diverted from the secretory pathway into a degradative pathway that occurs in the endoplasmic reticulum (3, 6). Regulated translocation of apoB across the endoplasmic reticulum could explain the posttranslational control of apoB secretion. In several studies, the amount of apoB that is secreted is less than the amount that is synthesized (5,(7)(8)(9)(10)(11)(12)(13)(14), leading to the conclusion that the unaccounted for apoB is degraded intracellularly. The consistent observation that in different types of cultured cells and perfused organs obtained from several species, a diverse group of hormones, nutritional states, stimulatory and inhibitory lipids, and mutations in the coding region of apoB alter the rate of apoB secretion by reciprocal changes in its rate of intracellular ...

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Section: Discussionmentioning

confidence: 99%

In HepG2 Cells, Translocation, Not Degradation, Determines the Fate of the de Novo Synthesized Apolipoprotein B

Bonnardel¹,

Davis²

1995

Journal of Biological Chemistry

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“…This result was similar to those of previous studies using fasting rats and cultured hepatocytes. Oleate increased incorporation of [ 3 H] leucine into VLDL apolipoprotein in fasted rats, and the increased incorporation of [ 3 H] leucine was mainly into VLDL-apoE [27,28]. In the human hapatoma cell line HepG2, enhanced association of apoE with large, apoBcontaining lipoproteins occurs when cellular lipogenesis and VLDL production are stimulated [12].…”

Section: Discussionmentioning

confidence: 99%

Bovine Apolipoprotein E in Plasma: Increase of ApoE Concentration Induced by Fasting and Distribution in Lipoprotein Fractions.

Takahashi

Sato

Itoh

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. Apolipoprotein E (apoE) is a protein constituent of lipoproteins, and acts as a receptor-binding ligand. Although the existence of bovine apoE in lipoprotein fractions has already been reported, quantitative studies on the changes of apoE in plasma and lipoprotein fractions are lacking. In the present study, an increase of a 38 kDa protein in the very low-density lipoprotein (VLDL) fraction obtained from fasted calves was detected. This 38 kDa protein was identified as bovine apoE by determination of the N-terminal amino acid sequence. Bovine apoE was purified and an enzyme-linked immunosorbent assay (ELISA) was developed. Using this system, the effect of fasting on the concentration of apoE in plasma and the distribution of apoE in lipoprotein fractions were investigated. After 3 days of fasting, the concentration of plasma apoE increased significantly (p<0.05) by 280 %, and was returned to the basal level by 3 days of refeeding. The lipoprotein fractions obtained from before and after fasting was separated by ultracentrifugation. ApoE was significantly increased in VLDL, low-density lipoprotein (LDL) and non-lipoprotein fractions by fasting (p<0.05). On the other hand, in highdensity lipoprotein (HDL) fractions obtained from both before and after fasting, the level of apoE was very low compared to the other fractions. These results suggested that bovine apoE contents in triglyceride-rich lipoproteins are modulated by nutritional treatment and closely associated with triglyceride-rich lipoprotein metabolism.

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“…Also, as compared to primary cells, they have additional energy requirements that may be partially met by using exogenous fatty acids as primarily fuel sources. Perhaps HepG2 cells resemble hepatocytes from fasted rats, which differ dramatically from hepatocytes from ad-lib fed rats by increasing their secretion of apoB in response to oleic acid (30).…”

Section: H)mentioning

confidence: 99%

N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes.

Wang¹,

Chen²,

Fisher³

1993

J. Clin. Invest.

130

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When rat hepatocytes were incubated with albumin complexed to the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), rather than to oleic acid (OA), the secretion of newly synthesized apoprotein B100 (apoB100) or B48 (apoB48) was reduced, despite stimulation of cellular triglyceride synthesis by all three fatty acids. When pulse-chase studies of apoB synthesis and secretion were performed in the presence of OA, EPA, or DHA, there were no significant changes in the initial synthetic rates of either apoB species. However, during the chase period, the total recovery of labeled apoB100 and apoB48 from the cell and medium was less in the n-3 fatty acid groups, so that by 150 min, approximately half as much labeled apoB was recovered as in the OA group. Overall, the decreased accumulation in medium of labeled apoB in the presence of EPA and DHA could be quantitatively accounted for by increased degradation of intracellular apoB. Thus, in the primary hepatocyte, apoB degradation is not constitutive, but can be regulated by n-3 fatty acids. (J. Clin. Invest. 1993.

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Effects of oleic acid on the biosynthesis of lipoprotein apoproteins and distribution into the very-low-density lipoprotein by the isolated perfused rat liver

Cited by 59 publications

References 48 publications

In HepG2 Cells, Translocation, Not Degradation, Determines the Fate of the de Novo Synthesized Apolipoprotein B

In HepG2 Cells, Translocation, Not Degradation, Determines the Fate of the de Novo Synthesized Apolipoprotein B

Bovine Apolipoprotein E in Plasma: Increase of ApoE Concentration Induced by Fasting and Distribution in Lipoprotein Fractions.

N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes.

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