Mechanisms of Macrophage Polarization in Insulin Signaling and Sensitivity

Orliaguet, Lucie; Dalmas, Élise; Drareni, Karima; Venteclef, Nicolas; Alzaïd, Fawaz

doi:10.3389/fendo.2020.00062

Cited by 93 publications

(79 citation statements)

References 213 publications

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“…Besides LPS and leptin, other factors that are elevated in the obese condition, such as saturated fatty acids and glucose, have been discussed as capable of polarizing macrophages towards an inflammatory phenotype but will not be discussed in this review. Instead, the reader is directed to several comprehensive reviews on this topic [38,76,[119][120][121][122][123][124][125][126].…”

Section: Pancreatic Stromal Macrophages In the Obese Statementioning

confidence: 99%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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Section: Pancreatic Stromal Macrophages In the Obese Statementioning

confidence: 99%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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“…We have also previously shown in vivo that macrophages that infiltrate into an injured liver during the recovery phase are crucial for the attenuation of inflammation and tissue repair ( 9 ). Macrophage polarization states are mainly divided into two types, the pro-inflammatory or classically activated M1 phenotype and the anti-inflammatory or alternatively activated M2 phenotype ( 10 ). LPS and/or IFN-γ can induce polarization to M1 macrophages that are capable of pro-inflammatory responses and produce pro-inflammatory molecules such as TNF-α and IL-6 ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

HGF-MET Signaling Shifts M1 Macrophages Toward an M2-Like Phenotype Through PI3K-Mediated Induction of Arginase-1 Expression

et al. 2020

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Backgrounds and Aims: Hepatocyte Growth Factor (HGF)-MET signaling is known to promote biological functions such as cell survival, cell motility, and cell proliferation. However, it is unknown if HGF-MET alters the macrophage phenotype. In this study, we aimed to study the effects of HGF-MET signaling on the M1 macrophage phenotype. Methods and Materials: Bone marrow-derived macrophages (BMDMs) isolated from mice were either polarized to an M1 phenotype by IFN-γ and LPS treatment or to an M2 phenotype by IL-4 treatment. Changes in M1 or M2 markers induced by HGF-MET signaling were evaluated. Mechanisms responsible for alternations in the macrophage phenotype and intracellular metabolism were analyzed. Results: c-Met was expressed especially in M1 macrophages polarized by treatment with IFN-γ and LPS. In M1 macrophages, HGF-MET signaling induced the expression of Arg-1 mRNA and secretion of IL-10 and TGF-β1 and downregulated the mRNA expression of iNOS, TNF- α, and IL-6 . In addition, activation of the PI3K pathway and inactivation of NFκB were also observed in M1 macrophages treated with HGF. The increased Arg-1 expression and IL-10 secretion were abrogated by PI3K inhibition, whereas, no changes were observed in TNF-α and IL-6 expression. The inactivation of NFκB was found to be independent of the PI3K pathway. HGF-MET signaling shifted the M1 macrophages to an M2-like phenotype, mainly through PI3K-mediated induction of Arg-1 expression. Finally, HGF-MET signaling also shifted the M1 macrophage intracellular metabolism toward an M2 phenotype, especially with respect to fatty acid metabolism. Conclusion: Our results suggested that HGF treatment not only promotes regeneration in epithelial cells, but also leads to tissue repair by altering M1 macrophages to an M2-like phenotype.

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“…These receptors span cell surface and intracellular membranes and they are ligated by damage-or pathogen-associated molecular patterns (DAMPs or PAMPs). In the case of metabolic diseases, stimulation is by DAMPs generated by dysmetabolism, such as fatty acids, hyperglycaemia, cellular senescence or other stress signals (30).…”

Section: Inflammatory Pathways In Adipose Tissuementioning

confidence: 99%

“…Macrophages play a key role in amplifying inflammation in the adipose microenvironment. Once activated, secreted cytokines act both locally and peripherally to increase inflammation and insulin resistance (30). Two main pathways are important actors of inflammation: the NLRP3 inflammasome and Interferon signalling.…”

Section: Inflammatory Pathways In Adipose Tissuementioning

confidence: 99%

Metabolic and Molecular Mechanisms of Macrophage Polarisation and Adipose Tissue Insulin Resistance

Orliaguet¹,

Ejlalmanesh²,

Alzaïd³

2020

Preprint

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Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

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Mechanisms of Macrophage Polarization in Insulin Signaling and Sensitivity

Cited by 93 publications

References 213 publications

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

HGF-MET Signaling Shifts M1 Macrophages Toward an M2-Like Phenotype Through PI3K-Mediated Induction of Arginase-1 Expression

Metabolic and Molecular Mechanisms of Macrophage Polarisation and Adipose Tissue Insulin Resistance

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