Insulin Resistance in Macrophages Alters Their Metabolism and Promotes an M2-Like Phenotype

Ieronymaki, Eleftheria; Theodorakis, Emmanouel M.; Lyroni, Konstantina; Vergadi, Eleni; Lagoudaki, Eleni; Al‐Qahtani, Ahmed; Aznaourova, Marina; Neofotistou-Themeli, Elpida; Eliopoulos, Aristides G.; Vaporidi, Katerina; Tsatsanis, Christos

doi:10.4049/jimmunol.1800065

Cited by 60 publications

(69 citation statements)

References 73 publications

(72 reference statements)

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“…In line with our findings, Amar et al showed that Porphyromonas gingivalis exposed PMs from mice with DIO produced less TNF, IL-1β, and IL-6 28. Similarly, Ieronymaki et al demonstrated that alveolar macrophages from insulin-resistant mice produced significantly less TNF after LPS exposure and expressed more arginase 1 29. They also showed a reduced inflammatory response after a cecal ligation and puncture (polymicrobial sepsis model) in diabetic mice.…”

Section: Discussionsupporting

confidence: 90%

Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Willemsen

Neele

Velden

et al. 2019

BMJ Open Diab Res Care

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IntroductionObesity is recognized as a risk factor for various microbial infections. The immune system, which is affected by obesity, plays an important role in the pathophysiology of these infections and other obesity-related comorbidities. Weight loss is considered the most obvious treatment for obesity. However, multiple studies suggest that the comorbidities of obesity may persist after weight loss. Deregulation of immune cells including adipose tissue macrophages of obese individuals has been extensively studied, but how obesity and subsequent weight loss affect immune cell function outside adipose tissue is not well defined.Research design and methodsHere we investigated the phenotype of non-adipose tissue macrophages by transcriptional characterization of thioglycollate-elicited peritoneal macrophages (PM) from mice with diet-induced obesity and type 2 diabetes (T2D). Subsequently, we defined the characteristics of PMs after weight loss and mimicked a bacterial infection by exposing PMs to lipopolysaccharide.Results and conclusionsIn contrast to the proinflammatory phenotype of adipose tissue macrophages in obesity and T2D, we found a deactivated state of PMs in obesity and T2D. Weight loss could reverse this deactivated macrophage phenotype. Anti-inflammatory characteristics of these non-adipose macrophages may explain why patients with obesity and T2D have an impaired immune response against pathogens. Our data also suggest that losing weight restores macrophage function and thus contributes to the reduction of immune-related comorbidities in patients.

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Section: Discussionsupporting

confidence: 90%

Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Willemsen

Neele

Velden

et al. 2019

BMJ Open Diab Res Care

View full text Add to dashboard Cite

show abstract

“…While not normally present within the CNS, macrophages are central mediators of neuroinflammation and contribute to inflammatory associated conditions, such as (Ieronymaki et al, 2019) neurotrauma and neurodegeneration (Hawkes and McLaurin, 2009). The effect of insulin on peripheral macrophages has been studied extensively, particularly in the context of obesity and diabetes (Olefsky and Glass, 2010).…”

Section: Macrophagesmentioning

confidence: 99%

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

et al. 2020

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Insulin is a hormone typically associated with pancreatic release and blood sugar regulation. The brain was long thought to be "insulin-independent," but research has shown that insulin receptors (IR) are expressed on neurons, microglia and astrocytes, among other cells. The effects of insulin on cells within the central nervous system are varied, and can include both metabolic and non-metabolic functions. Emerging data suggests that insulin can improve neuronal survival or recovery after trauma or during neurodegenerative diseases. Further, data suggests a strong antiinflammatory component of insulin, which may also play a role in both neurotrauma and neurodegeneration. As a result, administration of exogenous insulin, either via systemic or intranasal routes, is an increasing area of focus in research in neurotrauma and neurodegenerative disorders. This review will explore the literature to date on the role of insulin in neurotrauma and neurodegeneration, with a focus on traumatic brain injury (TBI), spinal cord injury (SCI), Alzheimer's disease (AD) and Parkinson's disease (PD).

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“…Basal mTORC1 activity in the insulin-resistant macrophages was high. The macrophages showed an M2-like phenotype, and reduced their responses to LPS (100). Dietary changes also impact the gut microbiome, which has been shown to be associated with immune activation as well as HIV/SIV vaccine efficacy and susceptibility to infection (26,101).…”

Section: Other Factor-induced Trained Immunitymentioning

confidence: 99%

“…Dietary changes also impact the gut microbiome, which has been shown to be associated with immune activation as well as HIV/SIV vaccine efficacy and susceptibility to infection (26,101). In this context, western diet, or insulin signaling/insulin resistance signals have been viewed as modulators of trained immunity (98,100,102). Overall, various populations around the world might have potentially different responses to vaccines as they have different genetic backgrounds, diets, and microbiomes, which can affect innate and trained immunity.…”

Section: Other Factor-induced Trained Immunitymentioning

confidence: 99%

Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development

Sui

Berzofsky

2020

Front. Immunol.

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Trained innate immunity has recently emerged as a novel concept of innate immune cells, such as myeloid cells, exhibiting immune memory, and nonspecific heterologous immunity to protect against infections. The memory and specificity are mediated by epigenetic, metabolic, and functional reprogramming of the myeloid cells and myeloid progenitors (and/or NK cells) in the bone marrow and peripheral tissues such as gut and lung mucosa. A variety of agents, such as BCG, viruses, and their components, as well as TLR agonists, and cytokines have been shown to be involved in the induction of trained immunity. Since these agents have been widely used in AIDS vaccine development as antigen delivery vectors or adjuvants, myeloid cell mediated trained immunity might also play an important role in protecting against mucosal AIDS virus transmission or in control of virus replication in the major gut mucosal reservoir. Here we review the trained innate immunity induced by these vectors/adjuvants that have been used in AIDS vaccine studies and discuss their role in mucosal vaccine efficacy and possible utilization in AIDS vaccine development. Delineating the protective effect of the trained innate immunity mediated by myeloid cells will guide the design of novel AIDS vaccines.

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Insulin Resistance in Macrophages Alters Their Metabolism and Promotes an M2-Like Phenotype

Cited by 60 publications

References 73 publications

Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development

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