Metabolic signatures linked to macrophage polarization: from glucose metabolism to oxidative phosphorylation

Boscá, Lisardo; González-Ramos, Silvia; Prieto, Patricia; Fernández‐Velasco, María; Mojena, Marina; Martı́n-Sanz, Paloma; Alemany, Susana

doi:10.1042/bst20150107

Cited by 60 publications

(62 citation statements)

References 45 publications

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“…Further studies will delineate the processes of selective targeting of proteins for S-NO modification and its effect on functional activity of the proteins. It is intriguing to note that (a) phagocytes activation and a decline in fatty acid metabolism where both of which were not spared from S-NO modification were differentially regulated in HF; (b) recent studies have indicated that upregulation of glucose metabolism promotes proliferation and activation of proinflammatory macrophages [38]. Our findings provide the first indication that a metabolic shift potentially contributes to proinflammatory state in progressive HF, to be verified in future studies.…”

Section: Discussionsupporting

confidence: 56%

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure

Koo

Spratt

Soman

et al. 2016

International Journal of Proteomics

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Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change | ≥1.5|, p ≤ 0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes' migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identified a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profiling identified ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top differentially abundant and S-NO-modified proteins, and these proteins were verified by Western blotting and ELISA in different set of HF subjects. We conclude that differential abundance and S-NO modification of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure.

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Section: Discussionsupporting

confidence: 56%

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure

Koo

Spratt

Soman

et al. 2016

International Journal of Proteomics

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“…58 Inhibition of glycolysis attenuates the adipocyte release of CCL2 in response to TNF-a or lipopolysaccharide, 59 demonstrating the connection between metabolism and inflammation. Pro-inflammatory (M1) macrophages rely on glycolysis for their metabolic demands.…”

Section: Atm Cytokines Productionmentioning

confidence: 99%

Properties and functions of adipose tissue macrophages in obesity

2018

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The expansion of adipose tissue (AT) in obesity is accompanied by the accumulation of immune cells that contribute to a state of low-grade, chronic inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs) represent the most abundant class of leukocytes in AT and are involved in the regulation of several regulatory physiological processes, such as tissue remodeling and insulin sensitivity. With progressive obesity, ATMs are key mediators of meta-inflammation, insulin resistance and impairment of adipocyte function. While macrophage recruitment from blood monocytes is a critical component of the generation of AT inflammation, new studies have revealed a role for ATM proliferation in the early stages of obesity and in sustaining AT inflammation. In addition, studies have revealed a more complex range of macrophage activation states than the previous M1/M2 model, and the existence of different macrophage profiles between human and animal models. This review will summarize the current understanding of the regulatory mechanisms of ATM function in relation to obesity, type 2 diabetes, depot of origin, and to other leukocytes such as AT dendritic cells, with hopes of emphasizing the regulatory nodes that can potentially be targeted to prevent and treat obesity-related metabolic disorders.

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“…In particular, upon IFNγ/LPS stimulation, the expression of PFK2 shifts from the liver isoform (L-PFK2) to the more active ubiquitous isoform (U-PFK2). U-PFK2 converts fructose-6-phosphate to fructose-2,6-biphosphate that in turn activates the glycolytic enzyme phosphofructo-1-kinase (PFK1) and consequently increases glycolytic flux (34, 35) because of its dominant kinase activity. Since the TCA cycle is truncated in M1 macrophages, lactate production regenerates the majority of the NAD + needed to sustain glycolysis.…”

Section: Metabolic Signature Of Macrophagesmentioning

confidence: 99%

Macrophage Metabolism As Therapeutic Target for Cancer, Atherosclerosis, and Obesity

et al. 2017

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Macrophages are not only essential components of innate immunity that contribute to host defense against infections, but also tumor growth and the maintenance of tissue homeostasis. An important feature of macrophages is their plasticity and ability to adopt diverse activation states in response to their microenvironment and in line with their functional requirements. Recent immunometabolism studies have shown that alterations in the metabolic profile of macrophages shape their activation state and function. For instance, to fulfill their respective functions lipopolysaccharides-induced pro-inflammatory macrophages and interleukin-4 activated anti-inflammatory macrophages adopt a different metabolism. Thus, metabolic reprogramming of macrophages could become a therapeutic approach to treat diseases that have a high macrophage involvement, such as cancer. In the first part of this review, we will focus on the metabolic pathways altered in differentially activated macrophages and link their metabolic aspects to their pro- and anti-inflammatory phenotype. In the second part, we will discuss how macrophage metabolism is a promising target for therapeutic intervention in inflammatory diseases and cancer.

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Metabolic signatures linked to macrophage polarization: from glucose metabolism to oxidative phosphorylation

Cited by 60 publications

References 45 publications

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure

Properties and functions of adipose tissue macrophages in obesity

Macrophage Metabolism As Therapeutic Target for Cancer, Atherosclerosis, and Obesity

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