Neutrophil extracellular traps (NETs) modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels

Freitas, Daniela Fernanda de; Colón, David F.; Silva, Rangel L.; Santos, Emanuele; Guimarães, Victor Hugo Dantas; Ribeiro, Guilherme Henrique Mendes; Paula, Alfredo Maurício Batista de; Guimarães, André Luiz Sena; Reis, Sidnei Tavares dos; Cunha, Fernando Q.; Antunes, Maísa Mota; Menezes, Gustavo B.; Santos, Sérgio Henrique Sousa

doi:10.1007/s11033-022-07157-y

Cited by 13 publications

(10 citation statements)

References 44 publications

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“…Furthermore, NETs play a potential role in the pathogenesis of some metabolic diseases, such as obesity and diabetes mellitus (DM). Studies have shown that NET levels in patients with obesity are higher than those in the healthy population ( 59 , 60 ), which is consistent with high levels of inflammatory cytokines in patients with obesity. Obesity is characterized by low-grade chronic inflammation, which underlies neutrophil activation and NET formation.…”

Section: Basis Of Netssupporting

confidence: 59%

“…Obesity is characterized by low-grade chronic inflammation, which underlies neutrophil activation and NET formation. Released NETs can, in turn, modulate inflammatory markers including IL-8, heat shock protein 90 (HSP90), and the E1 heat shock protein family (HSPE1), eventually contributing to metabolic profile alterations in obesity ( 60 ). Wong et al.…”

Section: Basis Of Netsmentioning

confidence: 99%

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The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside

Shao

Cao

et al. 2022

Front. Oncol.

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Neutrophil extracellular traps (NETs), products of neutrophil death when exposed to certain stimuli, were first proposed as a type of response to bacterial infection in infectious diseases. Since then, extensive studies have discovered its involvement in other non-infectious inflammatory diseases including thromboembolism, autoimmune diseases, and cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. NET formation is closely associated with tumorigenesis, progression, and metastasis in CRC. Therefore, the application of NETs in clinical practice as diagnostic biomarkers, therapeutic targets, and prognostic predictors has a promising prospect. In addition, therapeutics targeting NETs are significantly efficient in halting tumor progression in preclinical cancer models, which further indicates its potential clinical utility in cancer treatment. This review focuses on the stimuli of NETosis, its pro-tumorigenic activity, and prospective clinical utility primarily in but not limited to CRC.

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Section: Basis Of Netssupporting

confidence: 59%

Section: Basis Of Netsmentioning

confidence: 99%

The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside

Shao

Cao

et al. 2022

Front. Oncol.

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“…In the context of visceral obese fat tissue inflammation, there is also an increase of activated neutrophils. These cells release extracellular traps which interact with other immune cells to promote pro-inflammatory responses and possibly contribute to remodeling of the matrix because of the protease content of traps, in addition to promoting insulin resistance [113,114]. Obese visceral fat tissue also harbors increased numbers of mast cells [115] but it is not clear whether these cells promote or dampen inflammation [116].…”

Section: Influx Of Immune Cells Into Obese Visceral Fat Inflammation ...mentioning

confidence: 99%

Obese visceral fat tissue inflammation: from protective to detrimental?

Kolb

2022

BMC Med

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Obesity usually is accompanied by inflammation of fat tissue, with a prominent role of visceral fat. Chronic inflammation in obese fat tissue is of a lower grade than acute immune activation for clearing the tissue from an infectious agent. It is the loss of adipocyte metabolic homeostasis that causes activation of resident immune cells for supporting tissue functions and regaining homeostasis. Initially, the excess influx of lipids and glucose in the context of overnutrition is met by adipocyte growth and proliferation. Eventual lipid overload of hypertrophic adipocytes leads to endoplasmic reticulum stress and the secretion of a variety of signals causing increased sympathetic tone, lipolysis by adipocytes, lipid uptake by macrophages, matrix remodeling, angiogenesis, and immune cell activation. Pro-inflammatory signaling of adipocytes causes the resident immune system to release increased amounts of pro-inflammatory and other mediators resulting in enhanced tissue-protective responses. With chronic overnutrition, these protective actions are insufficient, and death of adipocytes as well as senescence of several tissue cell types is seen. This structural damage causes the expression or release of immunostimulatory cell components resulting in influx and activation of monocytes and many other immune cell types, with a contribution of stromal cells. Matrix remodeling and angiogenesis is further intensified as well as possibly detrimental fibrosis. The accumulation of senescent cells also may be detrimental via eventual spread of senescence state from affected to neighboring cells by the release of microRNA-containing vesicles. Obese visceral fat inflammation can be viewed as an initially protective response in order to cope with excess ambient nutrients and restore tissue homeostasis but may contribute to tissue damage at a later stage.

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“…Moreover, NETs concentrations correlated with the BMI [ 174 ]. In addition, recent bioinformatics studies found a strong relationship between obesity, inflammatory markers, such as TNF-α, IL-6, IL-8, heat shock protein 90 (HSP90), and NETs formation [ 175 , 176 ]. Moreover, it was also found that exercise reduces NETs [ 175 ].…”

Section: Neutrophils In Obesitymentioning

confidence: 99%

Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications

Uribe‐Querol

Rosales

2022

Cells

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Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state by producing cytokines and chemokines that can reach other parts of the body, creating a systemic inflammatory condition. In this review, we described the recent findings on the role of neutrophils during obesity and the initiation of inflammation. In addition, we discuss the involvement of neutrophils in the generation of obesity-related complications using diabetes as a prime example.

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Neutrophil extracellular traps (NETs) modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels

Cited by 13 publications

References 44 publications

The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside

The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside

Obese visceral fat tissue inflammation: from protective to detrimental?

Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications

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