scholarly journals The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity

2017 ◽  
Vol 61 (8) ◽  
pp. 1600824 ◽  
Author(s):  
Sergio Montserrat-de la Paz ◽  
Dolores Rodriguez ◽  
Magdalena P. Cardelo ◽  
Maria C. Naranjo ◽  
Beatriz Bermudez ◽  
...  
1991 ◽  
Vol 37 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Peter O Kwiterovich ◽  
Mahnaz Motevalli ◽  
Michae Miller ◽  
Paul S Bachorik ◽  
Stephanie D Kafonek ◽  
...  

Abstract Hyperapobetalipoproteinemia (hyperapoB), a familial lipoprotein disorder characterized by an increase in small, dense, low-density lipoprotein (LDL) particles, is strongly associated with coronary artery disease. There are two metabolic defects in hyperapoB: an increased synthesis of a very-low-density lipoprotein in liver, resulting in an overproduction of LDL, and a delayed clearance of post-prandial triglyceride and free fatty acids. To date, defects in the apolipoprotein B gene do not appear to explain the hyperapoB phenotype. Defect(s) in the uptake or intracellular metabolism of free fatty acids have been found in cells from hyperapoB patients. Three basic proteins (BPs)--BP I (Mr 14,000, pI 9.10), BP II (Mr 27,500, pI 8.48), and BP III (Mr 55,000, pI 8.73)--were isolated from normal human serum. Compared with normal fibroblasts, cultured hyperapoB fibroblasts incubated with BP I, which appears to be the same protein as acylation-stimulating protein (ASP), showed 50% less stimulation of triglyceride acylation and cholesterol esterification, whereas BP II markedly stimulated cholesteryl ester formation, and BP III caused no difference in response vs normal fibroblasts. However, in cultured normal human monocyte macrophages, BP III, but not BP I or BP II, stimulated cholesteryl esterification two- to threefold. BP I, BP II, and BP III may provide new insights into normal metabolism of lipids, lipoproteins, and free fatty acids and the pathophysiology of hyperapoB.


1992 ◽  
Vol 70 (8) ◽  
pp. 643-649 ◽  
Author(s):  
Andrew Howie ◽  
Yung-Sheng Huang ◽  
David F. Horrobin

Effects of supplementation of growth-promoting cholesterol on metabolism of the cytotoxic (n – 6) polyunsaturated fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 0 or 38.7 μM cholesterol. The rate of uptake and the distribution of metabolites of (n – 6) fatty acids (such as 18:2(n – 6), 18:3(n – 6), and20:3(n – 6), and20:4(n – 6)) were examined by adding radiolabelled fatty acid at a level of 1 μg/mL (3.3 μM for 20-carbon fatty acids and 3.6 μM for 18-carbon fatty acids). For assessing the cytotoxicity, (n – 6) fatty acids were added to medium at a concentration of 5 μg/mL (16.4 μM for 20-carbon fatty acids and 17.9 μM for 18-carbon fatty acids). Cholesterol supplementation suppressed the uptake of all (n – 6) fatty acids and reduced the cytotoxic effects of 18:2(n – 6), 20:3(n – 6), and 20:4(n – 6), but not 18:3(n – 6). In addition, cholesterol supplementation increased peroxide production and metabolism of (n – 6) fatty acids in U937 cells. Thus, the differential suppressive effect of cholesterol on the cytotoxicity of different fatty acids could not be attributed to an inhibitory effect on fatty acid Δ6- and Δ5-desaturation, or to an antioxidant effect on peroxide formation.Key words: (n – 6) fatty acid metabolism, cytotoxicity, peroxides.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Bridgette M Cumming ◽  
Kelvin W Addicott ◽  
John H Adamson ◽  
Adrie JC Steyn

How Mycobacterium tuberculosis (Mtb) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. Mtb infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, M. bovis BCG, or dead Mtb induced glycolytic phenotypes with greater flux. Furthermore, Mtb reduced the mitochondrial dependency on glucose and increased the mitochondrial dependency on fatty acids, shifting this dependency from endogenous fatty acids in uninfected cells to exogenous fatty acids in infected macrophages. We demonstrate how quantifiable bioenergetic parameters of the host can be used to accurately measure and track disease, which will enable rapid quantifiable assessment of drug and vaccine efficacy. Our findings uncover new paradigms for understanding the bioenergetic basis of host metabolic reprogramming by Mtb.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Claudia Nastasi ◽  
Marco Candela ◽  
Charlotte Menné Bonefeld ◽  
Carsten Geisler ◽  
Morten Hansen ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3139
Author(s):  
Carlos Vazquez-Madrigal ◽  
Soledad Lopez ◽  
Elena Grao-Cruces ◽  
Maria C. Millan-Linares ◽  
Noelia M. Rodriguez-Martin ◽  
...  

Dietary fatty acids have been demonstrated to modulate systemic inflammation and induce the postprandial inflammatory response of circulating immune cells. We hypothesized that postprandial triglyceride-rich lipoproteins (TRLs) may have acute effects on immunometabolic homeostasis by modulating dendritic cells (DCs), sentinels of the immunity that link innate and adaptive immune systems. In healthy volunteers, saturated fatty acid (SFA)-enriched meal raised serum levels of granulocyte/macrophage colony-stimulating factor GM-CSF (SFAs > monounsaturated fatty acids (MUFAs) = polyunsaturated fatty acids (PUFAs)) in the postprandial period. Autologous TRL-SFAs upregulated the gene expression of DC maturation (CD123 and CCR7) and DC pro-inflammatory activation (CD80 and CD86) genes while downregulating tolerogenic genes (PD-L1 and PD-L2) in human monocyte-derived DCs (moDCs). These effects were reversed with oleic acid-enriched TRLs. Moreover, postprandial SFAs raised IL-12p70 levels, while TRL-MUFAs and TRL-PUFAs increased IL-10 levels in serum of healthy volunteers and in the medium of TRL-treated moDCs. In conclusion, postprandial TRLs are metabolic entities with DC-related tolerogenic activity, and this function is linked to the type of dietary fat in the meal. This study shows that the intake of meals enriched in MUFAs from olive oil, when compared with meals enriched in SFAs, prevents the postprandial production and priming of circulating pro-inflammatory DCs, and promotes tolerogenic response in healthy subjects. However, functional assays with moDCs generated in the presence of different fatty acids and T cells could increase the knowledge of postprandial TRLs’ effects on DC differentiation and function.


2013 ◽  
Vol 24 (12) ◽  
pp. 2031-2039 ◽  
Author(s):  
Lourdes M. Varela ◽  
Almudena Ortega-Gomez ◽  
Sergio Lopez ◽  
Rocio Abia ◽  
Francisco J.G. Muriana ◽  
...  

Author(s):  
James K. Koehler ◽  
Steven G. Reed ◽  
Joao S. Silva

As part of a larger study involving the co-infection of human monocyte cultures with HIV and protozoan parasites, electron microscopic observations were made on the course of HIV replication and infection in these cells. Although several ultrastructural studies of the cytopathology associated with HIV infection have appeared, few studies have shown the details of virus production in “normal,” human monocytes/macrophages, one of the natural targets of the virus, and suspected of being a locus of quiescent virus during its long latent period. In this report, we detail some of the interactions of developing virons with the membranes and organelles of the monocyte host.Peripheral blood monocytes were prepared from buffy coats (Portland Red Cross) by Percoll gradient centrifugation, followed by adherence to cover slips. 90-95% pure monocytes were cultured in RPMI with 5% non-activated human AB serum for four days and infected with 100 TCID50/ml of HIV-1 for four hours, washed and incubated in fresh medium for 14 days.


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