Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Zhu, Xiao Feng; Tu, Yi-xuan; Chen, Hainan; Jackson, Ampadu O.; Patel, Vaibhav; Yin, Kai

doi:10.1002/dmrr.2993

Cited by 23 publications

(18 citation statements)

References 136 publications

(295 reference statements)

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“…ATMs acquire an M1-type pro-inflammatory phenotype in the inflamed adipose tissue during obesity (43–45). This M1-like phenotype includes expression of both oxidative and glycolytic genes (39, 46). M1-like ATMs express the scavenger receptor CD36, ATP-binding cassette transporter1 (ABCA1) and Perilipin (PLIN) as membrane markers, regulated by Peroxisome Proliferator-activated Receptor-γ(PPARγ), and do not express M1 markers (47).…”

Section: Introductionmentioning

confidence: 99%

Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes

et al. 2019

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Adaptation of the innate immune system has been recently acknowledged, explaining sustained changes of innate immune responses. Such adaptation is termed trained immunity. Trained immunity is initiated by extracellular signals that trigger a cascade of events affecting cell metabolism and mediating chromatin changes on genes that control innate immune responses. Factors demonstrated to facilitate trained immunity are pathogenic signals (fungi, bacteria, viruses) as well non-pathogenic signals such as insulin, cytokines, adipokines or hormones. These signals initiate intracellular signaling cascades that include AKT kinases and mTOR as well as histone methylases and demethylases, resulting in metabolic changes and histone modifications. In the context of insulin resistance, AKT signaling is affected resulting in sustained activation of mTORC1 and enhanced glycolysis. In macrophages elevated glycolysis readily impacts responses to pathogens (bacteria, fungi) or danger signals (TLR-driven signals of tissue damage), partly explaining insulin resistance-related pathologies. Thus, macrophages lacking insulin signaling exhibit reduced responses to pathogens and altered metabolism, suggesting that insulin resistance is a state of trained immunity. Evidence from Insulin Receptor as well as IGF1Receptor deficient macrophages support the contribution of insulin signaling in macrophage responses. In addition, clinical evidence highlights altered macrophage responses to pathogens or metabolic products in patients with systemic insulin resistance, being in concert with cell culture and animal model studies. Herein, we review the current knowledge that supports the impact of insulin signaling and other insulin resistance related signals as modulators of trained immunity.

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Section: Introductionmentioning

confidence: 99%

Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes

et al. 2019

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“…One of the treatment goals for diabetes is to normalize blood glucose to avoid or delay diabetes-related complications [1–4]. Both T1D and T2D are thought to develop via distinct and separate inflammatory responses that may share some common features, such as proinflammatory cells and cytokines [5–7]. It has been established that hyperglycemia plays a major part in this inflammatory process [8–14], which might adversely affect diabetes disease progression and complications.…”

Section: Introductionmentioning

confidence: 99%

Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection

Xia

Butfiloski

et al. 2018

Clinical Immunology

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The major metabolic feature of diabetes is hyperglycemia which has been linked to the diabetes inflammatory processes, and diabetes-related vulnerability to infection. In the present study, we assessed how glucose affected PBMCs in type I interferon (IFN) production and subsequent signaling. We found that the moderately elevated glucose promoted, and high glucose suppressed type I IFN production, respectively. Pre-exposure to high glucose rendered monocytes more sensitive to IFN-α stimulation with heightened signaling, whereas, instantaneous addition of high glucose did not exhibit such effect. Consistent with this finding, the mRNA levels of IFN-α-induced IRF-7 in PBMCs were positively correlated with HbA1c levels of diabetes patients. Additionally, we found that high glucose promoted the production of other proinflammatory cytokines/chemokines. This study suggests that hyperglycemia may affect the inflammatory process in diabetes via promoting proinflammatory cytokines, as well as the host defense against microbial infections through impeding type I IFN production and signaling.

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“…An imperative role of macrophage polarization has become increasingly implicated in the development of metabolic diseases including obesity and type 2 diabetes [11,12]. In general, there is an imbalance of macrophage polarization toward increase in M1 macrophages, leading to chronic inflammation and the propagation of metabolic dysfunction [11].…”

Section: Discussionmentioning

confidence: 99%

“…Abundant literature establishes an important role for macrophage polarization in the pathogenesis of metabolic diseases [11,12]. There is an imbalance in the ratio of M1/M2 macrophages in obesity and type 2 diabetes, leading to chronic inflammation and the propagation of metabolic dysfunction [11].…”

Section: Introductionmentioning

confidence: 99%

Asaronic Acid Inhibited Glucose-Triggered M2-Phenotype Shift Through Disrupting the Formation of Coordinated Signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK

Park

Kang

et al. 2020

Nutrients

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Macrophage polarization has been implicated in the pathogenesis of metabolic diseases such as obesity, diabetes, and atherosclerosis. Macrophages responsiveness to polarizing signals can result in their functional phenotype shifts. This study examined whether high glucose induced the functional transition of M2 macrophages, which was inhibited by asaronic acid, one of purple perilla constituents. J774A.1 murine macrophages were incubated with 40 ng/mL interleukin (IL)-4 or exposed to 33 mM glucose in the presence of 1-20 μΜ asaronic acid. In macrophages treated with IL-4 for 48 h, asaronic acid further accelerated cellular induction of the M2 markers of IL-10, arginase-1, CD163, and PPARγ via increased IL-4-IL-4Rα interaction and activated Tyk2-STAT6 pathway. Asaronic acid promoted angiogenic and proliferative capacity of M2-polarized macrophages, through increasing expression of VEGF, PDGF, and TGF-β. In glucose-loaded macrophages, there was cellular induction of IL-4, IL-4 Rα, arginase-1, and CD163, indicating that high glucose skewed naïve macrophages toward M2 phenotypes via an IL-4-IL-4Rα interaction. However, asaronic acid inhibited M2 polarization in diabetic macrophages in parallel with inactivation of Tyk2-STAT6 pathway and blockade of GLUT1-mediated metabolic pathway of Akt-mTOR-AMPKα. Consequently, asaronic acid deterred functional induction of COX-2, CTGF, α-SMA, SR-A, SR-B1, and ABCG1 in diabetic macrophages with M2 phenotype polarity. These results demonstrated that asaronic acid allayed glucose-activated M2-phenotype shift through disrupting coordinated signaling of IL-4Rα-Tyk2-STAT6 in parallel with GLUT1-Akt-mTOR-AMPK pathway. Thus, asaronic acid has therapeutic potential in combating diabetes-associated inflammation, fibrosis, and atherogenesis through inhibiting glucose-evoked M2 polarization.

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Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Cited by 23 publications

References 136 publications

Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes

Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes

Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection

Asaronic Acid Inhibited Glucose-Triggered M2-Phenotype Shift Through Disrupting the Formation of Coordinated Signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK

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