Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu; Ballantyne, Christie M.

doi:10.1210/jc.2016-2732

Cited by 42 publications

(69 citation statements)

References 43 publications

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“…Compared to the fasting state, a high-fat meal increased nile staining of lipids in all monocyte subsets after, but not before, MAT9001 treatment, and nile red staining of lipids in monocytes (subsets) in the postprandial state was similar before and after MAT9001 treatment (Figures 3A–3C). These findings were consistent with our previous observations that compared to obese subjects with hypertriglyceridemia and metabolic syndrome, control subjects with normal fasting TG levels had lower proportions of foamy monocytes in the fasting state but showed greater increases in postprandial nile red staining of lipids in monocytes (20). In contrast to MAT9001 treatment, treatment with EPA-EE did not significantly alter nile red levels in any monocyte subsets in either the fasting or postprandial state (Figures 3A–3C).…”

Section: Resultssupporting

confidence: 93%

“…Fasting and postprandial hypertriglyceridemia is associated with increased lipid content in monocytes and with formation of foamy monocytes in the circulation (15–17,20), which may contribute to ASCVD (19). Reductions in TG levels in subjects with hypertriglyceridemia by MAT9001 were associated with significantly reduced nile red levels, indicating less lipid, in both classical and intermediate monocytes in the fasting state compared to pretreatment (Figures 3A and 3B).…”

Section: Resultsmentioning

confidence: 99%

“…Foamy monocytes infiltrate into arterial walls and contribute to atherosclerosis (19,23). Hypertriglyceridemia in humans with obesity and metabolic syndrome is also associated with increased proportions of CD16 + intermediate or nonclassical monocytes (12,24) and with phenotypic changes in monocytes and subsets, including upregulation of adhesion molecules, toll-like receptors, inflammatory molecules, and oxidative stress (15,20,25–28). Moreover, postprandial elevations in triglyceride (TG) levels after a single high-fat meal promote monocyte (subset) phenotypic changes, particularly in subjects with elevated fasting TGs and metabolic syndrome (20).…”

Section: Introductionmentioning

confidence: 99%

“…Hypertriglyceridemia in humans with obesity and metabolic syndrome is also associated with increased proportions of CD16 + intermediate or nonclassical monocytes (12,24) and with phenotypic changes in monocytes and subsets, including upregulation of adhesion molecules, toll-like receptors, inflammatory molecules, and oxidative stress (15,20,25–28). Moreover, postprandial elevations in triglyceride (TG) levels after a single high-fat meal promote monocyte (subset) phenotypic changes, particularly in subjects with elevated fasting TGs and metabolic syndrome (20). Formation of foamy monocytes with phenotypic changes in hyperlipidemia may accelerate monocyte (subset) contributions to atherosclerosis and therefore serve as an important link between hypertriglyceridemia and the development of ASCVD (19,21,23).…”

Section: Introductionmentioning

confidence: 99%

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Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Perrard

Lian

Bobotas³

et al. 2017

Journal of Clinical Lipidology

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Background Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated fatty acids (PUFAs) reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. Objective We examined effects of n-3 PUFA treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [DPA] [MAT9001] versus EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. Methods Individuals with triglycerides 200–400 mg/dL were recruited. Subjects received two treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/day. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. Results Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the two treatments. Conclusions Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Perrard

Lian

Bobotas³

et al. 2017

Journal of Clinical Lipidology

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“…Foamy monocytes emerge early in the circulation of mice with hypercholesterolaemia 6 . In humans, even a single high-fat meal can increase lipid accumulation in circulating monocytes 8,9 . Importantly, foamy monocytes infiltrate into arterial walls and contribute to the development of atherosclerosis in mice with hypercholesterolaemia 6 .…”

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PCSK9 inhibitors and foamy monocytes in familial hypercholesterolaemia

Ballantyne

2017

Nat Rev Cardiol

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Accumulation of foam cells — macrophages with intracellular lipid droplets — in arterial walls is a hallmark of atherosclerosis. Bernelot Moens and colleagues report increases in circulating monocytes with intracellular lipid accumulation, associated CCR2 expression, and enhanced monocyte migration in patients with familial hypercholesterolaemia. These changes could be reversed by PCSK9-inhibitor treatment.

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Calibration‐free quantitative immunoassay by flow cytometry: Theoretical consideration and practical implementation for IgG antibody binding to CD14 receptors on human leukocytes

et al. 2018

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We propose a calibration-free method to determine the number of receptors per cell, as well as the direct and the reverse reaction rate constants for a single receptor. The method is based on the analysis of the temporal evolution of the cells mean fluorescent intensity measured by a flow cytometer during the ligand-receptor (antigen-antibody) binding under the conditions of their comparable concentrations. We developed the kinetic approach accounting both for the delay between the dilution and the measurement and for the practical duration of the measurement itself. The method was applied to determine thenumber of CD14 receptors on human blood mononuclear (granulocytes, monocytes, lymphocytes) cells of several donors. We also obtained the direct ( (5.6 ± 0.2) × 10 M min ) and reverse ( (1.3 ± 0.2) × 10 min ) rate constants of ligand-receptor interaction, and estimated the size of the binding site as b = 0.5 nm. The latter allows one to recalculate the rate constants for a different ligand, fluorescent label, medium viscosity, and/or temperature. The knowledge of the rate constants is essential for the calibration-free determination of the number of receptors per cell from a single kinetic curve of the cells mean fluorescence intensity.

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Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

Abstract: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation.

Cited by 42 publications

References 43 publications

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

PCSK9 inhibitors and foamy monocytes in familial hypercholesterolaemia

Calibration‐free quantitative immunoassay by flow cytometry: Theoretical consideration and practical implementation for IgG antibody binding to CD14 receptors on human leukocytes

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