Metabolic Modulation in Macrophage Effector Function

Diskin, Ciana; Pålsson-McDermott, Eva M.

doi:10.3389/fimmu.2018.00270

Cited by 244 publications

(245 citation statements)

References 160 publications

Supporting

Mentioning

231

Contrasting

Unclassified

Order By: Relevance

“…M2 macrophages prefer mitochondrial respiration, thus we performed mitochondrial stress assays in untreated macrophages (M0‐Ctr), M2 macrophages (M2‐Ctr) as well as dPGS treated macrophages (M2‐dPGS‐24h; M2‐dPGS‐7d). As described in other studies, anti‐inflammatory macrophages showed a significantly reinforced mitochondrial respiration (as indicated by OCR) ( Figure 5 A) . In contrast, dPGS treatment comprehensively decreased the mitochondrial function within the macrophages.…”

supporting

confidence: 83%

dPGS Regulates the Phenotype of Macrophages via Metabolic Switching

Reimann

Siddiqui

et al. 2019

Macromolecular Bioscience

View full text Add to dashboard Cite

The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L‐/P‐selectin or complement proteins leading to well described anti‐inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL‐10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro‐inflammatory phenotype in a metabolic pathway‐dependent manner.

show abstract

supporting

confidence: 83%

dPGS Regulates the Phenotype of Macrophages via Metabolic Switching

Reimann

Siddiqui

et al. 2019

Macromolecular Bioscience

View full text Add to dashboard Cite

show abstract

“…In the last decade, a large number of studies showed that M s when activated shift their metabolism from oxidative phosphorylation to aerobic glycolysis. 127,129,132 This change in intracellular metabolism also happens in tumor cells. 133 This phenomenon is called the Warburg Effect.…”

Section: Leptin and The Adipose Tissuementioning

confidence: 97%

“…In addition, M1 and M2 Mϕs are also distinctive metabolically. In the last decade, a large number of studies showed that Mϕs when activated shift their metabolism from oxidative phosphorylation to aerobic glycolysis . This change in intracellular metabolism also happens in tumor cells .…”

Section: Mϕ Metabolism—an Overviewmentioning

confidence: 99%

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

Monteiro

Pereira

Palhinha

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and Mϕs. Adipose tissue resident Mϕs (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both the JAK2‐STAT3 and the PI3K‐AKT‐mTOR pathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in Mϕs and how hyperleptinemia can contribute to the low‐grade systemic inflammation in obesity.

show abstract

“…Blocking oxidative metabolism abrogates anti-inflammatory macrophage function without affecting the proinflammatory state (Ghesquiere, Wong, Kuchnio, & Carmeliet, 2014). For a detailed description of both classical and emerging pathways, including metabolic pathways, relevant for macrophage phenotypes we refer the readers to recent excellent reviews (Amici et al, 2017;Diskin & Palsson-McDermott, 2018).…”

Section: Introductionmentioning

confidence: 99%

How to reprogram microglia toward beneficial functions

Fumagalli

Lombardi

Gressèns

et al. 2018

Glia

View full text Add to dashboard Cite

Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro-regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.

show abstract

Metabolic Modulation in Macrophage Effector Function

Cited by 244 publications

References 160 publications

dPGS Regulates the Phenotype of Macrophages via Metabolic Switching

dPGS Regulates the Phenotype of Macrophages via Metabolic Switching

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

How to reprogram microglia toward beneficial functions

Contact Info

Product

Resources

About