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 The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

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.

scholarly journals Heterogeneity of very-low-density lipoprotein remnants bound and taken up by liver of starved rat in vivo

1983 ◽  
Vol 212 (1) ◽  
pp. 173-182
Author(s):  
M M Ittmann ◽  
C Cooper
Keyword(s):  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Water Soluble ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Density Range ◽  
Mean Diameter ◽  
Vldl Remnant

Very-low-density lipoprotein (VLDL), labelled in vivo with [9,10-3H]oleate, was taken up rapidly by liver after injection in vivo. Initially, radioactive lipoprotein remnants in the VLDL density range were present in liver as a bound extracellular pool that could be released by perfusion with polyphosphate or heparin. The bound remnant showed a decrease in mean diameter and an increased proportion of cholesteryl ester as a function of time after injection. When VLDL of different mean diameters was injected, it was found that: (1) total uptake by liver was independent of diameter; (2) small VLDL was not taken up more rapidly than large VLDL; and (3) Large VLDL lost no more triacylglycerol before binding than did small VLDL and larger species of mean diameter greater than 40 nm were bound. It is concluded that there is no unique VLDL remnant taken up by liver in vivo. When livers were perfused after binding radioactive VLDL in vivo, the lipoprotein was metabolized, with the production of water-soluble products, and this metabolism was inhibited by chloroquine.

scholarly journals Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic Very Low-Density Lipoprotein Production in Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2169-2174 ◽  
Author(s):  
Wan Huang ◽  
Anantha Metlakunta ◽  
Nikolas Dedousis ◽  
Heidi K. Ortmeyer ◽  
Maja Stefanovic-Racic ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Saline Control ◽  
Acid Oxidation ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Vldl Metabolism

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P < 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P < 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P < 0.01), increased liver TGs (∼20%, P < 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P < 0.01) and increased fatty acid oxidation (∼50%, P < 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles.

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