Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells

2005 ◽  
Vol 43 (3) ◽  
Author(s):  
Sebely Pal ◽  
Ryusuke Takechi ◽  
Suleen S. Ho
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Palmitic Acid ◽  
Conjugated Linoleic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Cells ◽  
The Body ◽  
Low Density

AbstractStudies in healthy humans have shown that consumption of conjugated linoleic acid (CLA) significantly reduced very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) blood concentrations. We propose that decreased concentrations are due to the inhibition of VLDL production and secretion [measured by apolipoprotein B100 (apoB100)] from the liver. To investigate the effects of a mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were incubated for 24h with 50μmol/L of the different fatty acids. Effects of CLA were compared to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic acid) and no treatment (control). HepG2-cell apoB100 levels were measured using Western blotting. ApoB100 secretion was significantly decreased in cells treated with CLA (44%, p<0.005) compared to control cells and those enriched with palmitic acid. Treatment of cells with CLA also decreased intracellular cholesterol levels. Collectively, these results demonstrate that CLA reduces apoB100 production and secretion compared to saturated and polyunsaturated fatty acids, possibly by limiting the availability of free cholesterol (required for apoB100 production). A reduction in apoB100 production in the body would decrease the levels of VLDL and atherogenic LDL and thus reduce the risk of developing cardiovascular disease.

scholarly journals Staphylococcus aureusUtilizes Host-Derived Lipoprotein Particles as Sources of Fatty Acids

2018 ◽  
Vol 200 (11) ◽  
Author(s):  
Phillip C. Delekta ◽  
John C. Shook ◽  
Todd A. Lydic ◽  
Martha H. Mulks ◽  
Neal D. Hammer
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Low Density ◽  
Content Type ◽  
Lipoprotein Particles ◽  
Bacterial Fatty Acid

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects ofS. aureusphysiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis (FASII) pathway. FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL), represent a potentially rich source of exogenous fatty acids forS. aureusduring infection. We sought to test the ability of LDLs to serve as a fatty acid source forS. aureusand show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth ofS. aureusfatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids forS. aureusduring infection.IMPORTANCEInhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused byS. aureusand other human pathogens. However,S. aureusincorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the clinical utility of targeting bacterial fatty acid synthesis is debated. Moreover, the fatty acid reservoir(s) exploited byS. aureusis not well understood. Human low-density lipoprotein particles represent a particularly abundantin vivosource of fatty acids and are present in tissues thatS. aureuscolonizes. Herein, we establish thatS. aureusis capable of utilizing the fatty acids present in low-density lipoproteins to bypass both chemical and genetic inhibition of fatty acid synthesis. These findings imply thatS. aureustargets LDLs as a source of fatty acids during pathogenesis.

Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion

1985 ◽  
Vol 248 (6) ◽  
pp. E732-E740 ◽  
Author(s):  
R. R. Wolfe ◽  
J. H. Shaw ◽  
M. J. Durkot
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Co2 Production ◽  
Acid Oxidation ◽  
Direct Oxidation ◽  
Total Rate ◽  
Gram Negative

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.

scholarly journals Extracellular fatty acids are not utilized directly for the synthesis of very-low-density lipoprotein in primary cultures of rat hepatocytes

1992 ◽  
Vol 287 (3) ◽  
pp. 749-753 ◽  
Author(s):  
G F Gibbons ◽  
S M Bartlett ◽  
C E Sparks ◽  
J D Sparks
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Acid Concentration ◽  
Low Density Lipoprotein ◽  
Primary Cultures ◽  
Density Lipoprotein ◽  
Fatty Acid Concentration ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Extracellular Fatty Acid

In hepatocytes cultured in the presence of oleate (initial concn. 0.75 mM), the secretion of very-low-density lipoprotein (VLDL) triacylglycerol and, to a lesser extent, apoprotein B (apoB) increased with time, whereas there was a large decline in the extracellular concentration of fatty acid. There was thus no synchronous relationship between the extracellular fatty acid concentration and the secretion of VLDL. Rather, the appearance of VLDL in the medium was dependent on the intracellular triacylglycerol concentration. At a given concentration of extracellular fatty acid, cells depleted of triacylglycerol secreted less VLDL triacylglycerol and apoB than did control cells. A similar pattern was observed for triacylglycerol newly synthesized from extracellular [3H]oleate. By contrast, the synthesis and output of ketone bodies were directly dependent on the fatty acid concentration of the medium. These results suggest that, at least for oleic acid, extracellular fatty acids are not utilized directly for VLDL assembly, but first enter a temporary intracellular storage pool of triacylglycerol, which is the immediate precursor of secreted triacylglycerol. The size of this pool then determines the rate of secretion of VLDL triacylglycerol apoB. Ketogenesis, on the other hand, relies mainly on the direct utilization of extracellular fatty acids.

scholarly journals Contribution of very low-density lipoprotein triglyceride fatty acids to postabsorptive free fatty acid flux in obese humans

Metabolism ◽  
2014 ◽  
Vol 63 (1) ◽  
pp. 137-140 ◽  
Author(s):  
Nikki C. Bush ◽  
Jessica M. Triay ◽  
Nicola W. Gathaiya ◽  
Kazanna C. Hames ◽  
Michael D. Jensen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density

scholarly journals The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease

2021 ◽  
Author(s):  
Erik Froyen
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Linoleic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Risk Markers ◽  
Cvd Risk ◽  
Acid Consumption

Cardiovascular disease (CVD) is the number one contributor to death in the United States and worldwide. Lipid risk markers for CVD include high serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein (a), and triglycerides, as well as low serum concentrations of high-density lipoprotein cholesterol (HDL-C). Additional factors to assess CVD risk include apolipoprotein A (associated with HDL) and apolipoprotein B (associated with LDL). A suggested dietary strategy to decrease these risk factors is to replace a portion of saturated fatty acids with unsaturated fatty acids – especially polyunsaturated fatty acids (PUFAs). One PUFA, in particular, is the essential omega-6 PUFA linoleic acid, which has been demonstrated to affect these CVD risk markers. Therefore, this chapter will discuss the effects of linoleic acid consumption on lipid risk markers for CVD in healthy individuals, the associated mechanisms, and dietary recommendations to decrease CVD risk.

scholarly journals Fatty Acid Profile of Major Lipid Classes in Plasma Lipoproteins of Patients with Friedreich's Ataxia — Demonstration of a Low Linoleic Acid Content most evident in the Cholesterol-Ester Fraction

1979 ◽  
Vol 6 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Jean Davignon ◽  
Y.S. Huang ◽  
J.P. Wolf ◽  
A. Barbeau
Keyword(s):  
Fatty Acid ◽  
Linoleic Acid ◽  
Fatty Acid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Lipid Classes ◽  
Low Density ◽  
Total Plasma

SummaryStudies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/All ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL· There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglycéride (TG) fraction showed only an increase in palmi t oleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.

scholarly journals Lipogenesis and the synthesis and secretion of very low density lipoprotein by avian liver cells in nonproliferating monolayer culture. Hormonal effects.

1977 ◽  
Vol 73 (2) ◽  
pp. 332-353 ◽  
Author(s):  
D M Tarlow ◽  
P A Watkins ◽  
R E Reed ◽  
R S Miller ◽  
E E Zwergel ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Liver Cells ◽  
Leucine Incorporation ◽  
Very Low Density Lipoprotein ◽  
Low Density

The nonproliferating chicken liver cell culture system described yields cell monolayers with morphological and lipogenic properties characteristic of the physiological-nutritional state of donor animals. Synthesis and secretion of fatty acid, cholesterol, and very low density lipoprotein (VLDL) occur at in vivo rates and respond to hormones and agents which affect these processes in vivo. Cells derived from fed chickens maintain high rates of synthesis of fatty acid and cholesterol for several days if insulin is present in the medium. High rates of fatty acid synthesis are correlated with the appearance of membrane-enclosed triglyceride-rich vesicles in the cytoplasm; deletion of insulin causes a decrease (T1/2 = 22 h) in fatty acid synthetic activity. Addition of glucagon or cyclic AMP (cAMP) causes an immediate cessation of fatty acid synthesis and blocks the appearance of the triglyceride-rich vesicles. Fatty acid synthesis in liver cells prepared from fasted chickens is less than 5% that of cells from fed animals. After 2-3 days in culture with serum-free medium containing insulin +/- triiodothyronine, fatty acid synthesis is restored to normal; glucagon or dibutyryl cAMP blocks this recovery. Liver cells derived from estradiol-treated chickens synthesize and secrete VLDL for at least 48 h in culture. Electron micrographs of these cells reveal more extensive development of the rough endoplasmic reticulum and Golgi complex compared to cells from untreated chickens. Whereas [3H]leucine incorporation into total protein is unaffected by estrogen treatment, [3H]leucine incorporation into cellular and secreted immunoprecipitable VLDL is markedly increased indicating specific activation of VLDL apopeptide synthesis; 8-10% of the labeled protein synthesized and secreted is VLDL. Dodecyl sulfate-acrylamide gel electrophoresis of immunoprecipitated 3H-VLDL reveals three major apopepetides of 300,000, 11,000, and 8,000 daltons corresponding to those of purified chicken VLDL.

scholarly journals Origin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid

1996 ◽  
Vol 320 (2) ◽  
pp. 673-679 ◽  
Author(s):  
David WIGGINS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cell Protein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Exogenous Fatty Acid ◽  
Cellular Phospholipid

When rat hepatocytes were cultured for 24 h in the absence of exogenous fatty acid, the amount of very-low-density lipoprotein (VLDL) triacylglycerol (TAG) secreted (114±14 µg/mg of cell protein) could not be accounted for by the mass of TAG lost from the cells (29±6.1 µg/mg of cell protein) during this period (n = 12). Of the balance (85±14 µg/mg; 94±15 nmol/mg), a maximum of only 37 nmol/mg of cell protein of TAG could be accounted for by fatty acids synthesized de novo. When labelled exogenous oleate (initial concentration, 0.75 mM) was present in the culture medium, the net gain in cellular plus VLDL TAG (253±38 µg/mg of cell protein per 24 h) was greater than that contributed by the exogenous fatty acid (155±18.2 µg/mg of cell protein, n = 5). Again, the balance (98.8±18.2 µg/mg of cell protein per 24 h) was too great to be accounted for by fatty acid synthesis de novo. In experiments in which cellular glycerolipids were prelabelled with [9,10(n)-3H]oleic acid, following removal of the labelled fatty acid, there was a net increase in labelled cellular plus VLDL TAG over the next 24 h. That cellular phospholipids are the source of a substantial part of the excess TAG synthesized is supported by the following evidence. (1) The loss of prelabelled cellular phospholipid during culture was greater than could be accounted for by secretion into the medium. (2) During culture of cells prelabelled with 1,2-di-[1-14C]palmitoyl phosphatidylcholine, a substantial amount of label was secreted as VLDL TAG. (3) In pulse–chase experiments, the kinetics of labelled phospholipid turnover were consistent with conversion into a non-phospholipid pool. The enzymology involved in the transfer of phospholipid fatty acids into TAG is probably complex, but the present results suggest that this pathway may represent an important route by which extracellular fatty acids are channelled into VLDL TAG.

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