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

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.

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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.045 ◽

2005 ◽

Vol 43 (3) ◽

Cited By ~ 9

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.

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Effect of atorvastatin and rosuvasta tin on the fatty acid spectrum of lymphocyte membranes in patients with unstable angina

Reports of the National Academy of Sciences of Ukraine ◽

10.15407/dopovidi2020.11.092 ◽

2020 ◽

pp. 92-95

Author(s):

T.V. Bogdan ◽

Keyword(s):

Cardiovascular Disease ◽

Fatty Acids ◽

Fatty Acid ◽

Unstable Angina ◽

Unsaturated Fatty Acids ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Membrane Phospholipids ◽

Stabilization Of Membranes ◽

Dynamic Structures

Numerous studies have demonstrated the superiority of rosuvastatin over other statins in the treatment of cardiovascular disease. It has been proven that rosuvastatin is more effectively lowers low-density lipoprotein cholesterol in patients with cardiovascular disease than other members of this drug group. Despite the known mechanisms of action of statins on blood lipids, their effective use in patients with cardiovascular disease, as well as side effects, the influence of these drugs on the fatty acid spectrum of lymphocyte (LC) membrane phospholipids in patients with ischemic heart disease remains unexplored. The results of the studies cited in the article indicate that, in patients with unstable angina who received the therapy that included rosuvastatin, unlike patients receiving the basic treatment with atorvastatin, the relative phosphate lipid contents of palmitic, stearic, and stearin arachidonic polyunsaturated fatty acids and the amount of unsaturated fatty acids are normalized, which testifies to the stabilization of membranes as dynamic structures.

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Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition

Molecular and Cellular Biology ◽

10.1128/mcb.22.23.8204-8214.2002 ◽

2002 ◽

Vol 22 (23) ◽

pp. 8204-8214 ◽

Cited By ~ 141

Author(s):

Linda E. Hammond ◽

Patricia A. Gallagher ◽

Shuli Wang ◽

Sylvia Hiller ◽

Kimberly D. Kluckman ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Saturated Fatty Acids ◽

Low Density Lipoprotein ◽

Fatty Acid Content ◽

Density Lipoprotein ◽

Positional Analysis ◽

Triacylglycerol Content ◽

Hepatic Triacylglycerol

ABSTRACT Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT−/− mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT−/− liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT−/− liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.

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

Endocrinology ◽

10.1210/en.2008-1271 ◽

2009 ◽

Vol 150 (5) ◽

pp. 2169-2174 ◽

Cited By ~ 13

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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The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: II. The plasma total and low-density lipoprotein cholesterol response of individual fatty acids

Metabolism ◽

10.1016/0026-0495(93)90183-o ◽

1993 ◽

Vol 42 (1) ◽

pp. 130-134 ◽

Cited By ~ 42

Author(s):

Janice Derr ◽

P.M. Kris-Etherton ◽

Thomas A. Pearson ◽

Frances H. Seligson

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Plasma Lipids ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Fatty Acid Saturation

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

Journal of Bacteriology ◽

10.1128/jb.00728-17 ◽

2018 ◽

Vol 200 (11) ◽

Cited By ~ 18

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.

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Exogenous polyunsaturated fatty acids (PUFAs) promote changes in growth, phospholipid composition, membrane permeability and virulence phenotypes in Escherichia coli

BMC Microbiology ◽

10.1186/s12866-020-01988-0 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Joshua L. Herndon ◽

Rachel E. Peters ◽

Rachel N. Hofer ◽

Timothy B. Simmons ◽

Steven J. Symes ◽

...

Keyword(s):

Escherichia Coli ◽

Fatty Acids ◽

Fatty Acid ◽

Membrane Permeability ◽

Phospholipid Composition ◽

Acid Oxidation ◽

Gram Negative Bacteria ◽

Membrane Phospholipids ◽

Gram Negative ◽

E Coli

Abstract Background The utilization of exogenous fatty acids by Gram-negative bacteria has been linked to many cellular processes, including fatty acid oxidation for metabolic gain, assimilation into membrane phospholipids, and control of phenotypes associated with virulence. The expanded fatty acid handling capabilities have been demonstrated in several bacteria of medical importance; however, a survey of the polyunsaturated fatty acid responses in the model organism Escherichia coli has not been performed. The current study examined the impacts of exogenous fatty acids on E. coli. Results All PUFAs elicited higher overall growth, with several fatty acids supporting growth as sole carbon sources. Most PUFAs were incorporated into membrane phospholipids as determined by Ultra performance liquid chromatography-mass spectrometry, whereas membrane permeability was variably affected as measured by two separate dye uptake assays. Biofilm formation, swimming motility and antimicrobial peptide resistance were altered in the presence of PUFAs, with arachidonic and docosahexaenoic acids eliciting strong alteration to these phenotypes. Conclusions The findings herein add E. coli to the growing list of Gram-negative bacteria with broader capabilities for utilizing and responding to exogenous fatty acids. Understanding bacterial responses to PUFAs may lead to microbial behavioral control regimens for disease prevention.

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Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.5.e798 ◽

1998 ◽

Vol 275 (5) ◽

pp. E798-E805 ◽

Cited By ~ 22

Author(s):

Labros S. Sidossis ◽

Bettina Mittendorfer ◽

Eric Walser ◽

David Chinkes ◽

Robert R. Wolfe

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Fatty Acid Uptake ◽

Secretion Rate ◽

Acid Oxidation ◽

Acid Uptake ◽

Hepatic Triacylglycerol

The effect of hyperglycemia (∼8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 ± 0.2 and 2.2 ± 0.9 μmol ⋅ kg−1⋅ min−1in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 ± 0.04 to 0.2 ± 0.05 μmol ⋅ kg−1⋅ min−1( P < 0.05). Hepatic TG secretion increased from 0.35 ± 0.07 μmol ⋅ kg−1⋅ min−1in the basal state to 0.53 ± 0.11 μmol ⋅ kg−1⋅ min−1after 15 h of hyperglycemia ( P< 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 ± 0.06 to 0.43 ± 0.05 mmol/l during the clamp ( P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.

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

Biochemical Journal ◽

10.1042/bj2870749 ◽

1992 ◽

Vol 287 (3) ◽

pp. 749-753 ◽

Cited By ~ 68

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.

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