Macrophages and lipid metabolism

Remmerie, Anneleen; Scott, Charlotte

doi:10.1016/j.cellimm.2018.01.020

Cited by 318 publications

(284 citation statements)

References 212 publications

(324 reference statements)

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“…For example, M1 macrophages synthesize lipids and produce inflammatory lipid mediators like eicosanoids while M2 macrophages tend to take up and oxidize lipids. 34 This relationship appears in the context of obesity as well. Chawla et al demonstrated that the transcription factor peroxisome proliferator-activated receptor (PPAR) gamma is required for alternative activation of ATMs and that mice deficient in macrophage PPARγ have accelerated development of obesity and IR.…”

Section: Polarizationmentioning

confidence: 99%

Adipose tissue macrophages: Unique polarization and bioenergetics in obesity

Caslin

Bhanot

Bolus

et al. 2020

Immunological Reviews

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Macrophages comprise a majority of the resident immune cells in adipose tissue (AT) and regulate both tissue homeostasis in the lean state and metabolic dysregulation in obesity. Since the AT environment rapidly changes based upon systemic energy status, AT macrophages (ATMs) must adapt phenotypically and metabolically. There is a distinct dichotomy in the polarization and bioenergetics of in vitro models, with M2 macrophages utilizing oxidative phosphorylation (OX PHOS) and M1 macrophages utilizing glycolysis. Early studies suggested differential polarization of ATMs, with M2‐like macrophages predominant in lean AT and M1‐like macrophages in obese AT. However, recent studies show that the phenotypic plasticity of ATMs is far more complicated, which is also reflected in their bioenergetics. Multiple ATM populations exist along the M2 to M1 continuum and appear to utilize both glycolysis and OX PHOS in obesity. The significance of the dual fuel bioenergetics is unclear and may be related to an intermediate polarization, their buffering capacity, or the result of a mixed population of distinct polarized ATMs. Recent evidence also suggests that ATMs of lean mice serve as a substrate buffer or reservoir to modulate lipid, catecholamine, and iron availability. Furthermore, recent models of weight loss and weight cycling reveal additional roles for ATMs in systemic metabolism. Evaluating ATM phenotype and intracellular metabolism together may more accurately illuminate the consequences of ATM accumulation in obese AT, lending further insight into obesity‐related comorbidities in humans.

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Section: Polarizationmentioning

confidence: 99%

Adipose tissue macrophages: Unique polarization and bioenergetics in obesity

Caslin

Bhanot

Bolus

et al. 2020

Immunological Reviews

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“…Macrophages ingest LDL, VLDL and oxidized lipoproteins becoming the classic foam cell. In dyslipidaemic states, such as with high levels of VLDL and LDL, excessive lipid uptake by macrophages is enhanced and together with defective cholesterol trafficking from the atherosclerotic lesion, promotes a pro‐inflammatory M1 macrophage phenotype and resultant accelerated atherogenesis . Pro‐inflammatory states frequently accompany a pro‐thrombotic phenotype as evidenced by increased platelet aggregation and a pro‐coagulopathic tendencies, as evidenced by increased levels of fibrinogen and plasminogen activator inhibitor‐1 …”

Section: Aetiology and Pathophysiologymentioning

confidence: 99%

The importance of dyslipidaemia in the pathogenesis of cardiovascular disease in people with diabetes

Gonna

Ray

2019

Diabetes Obesity Metabolism

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Atherosclerotic cardiovascular events are the leading cause of mortality and morbidity in those with diabetes. A key contributor to the development of atherosclerosis in this population is the presence of a particularly atherogenic lipid profile often referred to as ‘Diabetic Dyslipidemia’. This profile is characterized by elevated triglycerides, triglyceride‐rich lipoproteins, small dense LDL particles, and reduced HDL levels. This article reviews the underlying aetiology and pathophysiology of this dyslipidaemia and atherosclerosis in those with diabetes, provides insights from epidemiological and genetic studies, and current cardiovascular risk reducing interventions including novel therapies such as PCSK‐9 inhibitors.

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“…Consequently, it must be shuttled to the endoplasmic reticulum (ER) to be esterified and stored in lipid droplets, or effluxed from the cell via transporters such as the ATP-binding cassette transporter, ABCA1 (Remmerie and Scott, 2018). When there is too much free cholesterol in the ER the esterification machinery can become overwhelmed leading to the accumulation of free cholesterol, toll-like receptor (TLR) signaling, and nuclear factor kappa-light-chain enhancer (NF-kB) activation (Remmerie and Scott, 2018). This inflammatory signaling, combined with ER stress and the accumulation of free cholesterol, can cause cell death by apoptosis (Remmerie and Scott, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…When there is too much free cholesterol in the ER the esterification machinery can become overwhelmed leading to the accumulation of free cholesterol, toll-like receptor (TLR) signaling, and nuclear factor kappa-light-chain enhancer (NF-kB) activation (Remmerie and Scott, 2018). This inflammatory signaling, combined with ER stress and the accumulation of free cholesterol, can cause cell death by apoptosis (Remmerie and Scott, 2018). Apoptotic macrophages must be cleared by neighboring macrophages which may themselves have stressed lipid metabolism and an impaired ability to perform this clearance function.…”

Section: Introductionmentioning

confidence: 99%

Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism

Chung

Frye

Zbesko

et al. 2018

Preprint

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The response to ischemic injury in the brain is different to the response to ischemic injury in other organs and tissues. Almost exclusive to the brain, and for unknown reasons, dead tissue liquefies in response to ischemia by the process of liquefactive necrosis. However, the data we present here indicate that at the macroscopic, microscopic, and molecular level, liquefactive necrosis strongly resembles atherosclerosis. We show that chronic stroke infarcts contain foamy macrophages, cholesterol crystals, high levels of osteopontin and matrix metalloproteinases, and a similar cytokine profile to atherosclerosis. Excessive cholesterol loading of macrophages is a principal driver of atherosclerosis. Therefore, because cholesterol is an important structural component of myelin, liquefactive necrosis in response to stroke may be caused by an inflammatory response to myelin debris that is prolonged by the formation of cholesterol crystals within macrophages. We propose that this results in the chronic production of high levels of proteases, which in a partially osteopontin dependent mechanism, causes secondary neurodegeneration and encephalomalacia of the surrounding tissue. In support of this, we show that genetically ablating osteopontin substantially reduces the production of degradative enzymes following stroke, reduces secondary neurodegeneration, and improves recovery.These findings suggest that treatments that prevent atherosclerosis or target the regression of All rights reserved. No reuse allowed without permission.

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Macrophages and lipid metabolism

Abstract: HighlightsThe transcriptional signature of Kupffer cells & Alveolar macrophages are enriched for lipid metabolism genes.Lipid metabolism may control macrophage phenotype.Dysregulated lipid metabolism in macrophages contributes to disease pathology.

Cited by 318 publications

References 212 publications

Adipose tissue macrophages: Unique polarization and bioenergetics in obesity

Adipose tissue macrophages: Unique polarization and bioenergetics in obesity

The importance of dyslipidaemia in the pathogenesis of cardiovascular disease in people with diabetes

Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism

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