scholarly journals Obesity and COVID-19: immune and metabolic derangement as a possible link to adverse clinical outcomes

2020 ◽  
Vol 319 (1) ◽  
pp. E105-E109 ◽  
Author(s):  
Emmanouil Korakas ◽  
Ignatios Ikonomidis ◽  
Foteini Kousathana ◽  
Konstantinos Balampanis ◽  
Aikaterini Kountouri ◽  
...  
Keyword(s):  
Strong Association ◽  
Host Cells ◽  
Low Grade ◽  
Metabolic Derangement ◽  
Innate And Adaptive Immunity ◽  
Monocyte Chemoattractant ◽  
Pyrin Domain ◽  
And Function ◽  
Low Grade Inflammation ◽  
Receptor Family

Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as “cytokine storm,” while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

scholarly journals The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1552
Author(s):  
Maria Sebastian-Valverde ◽  
Giulio M. Pasinetti
Keyword(s):  
Nlrp3 Inflammasome ◽  
Low Grade ◽  
Cellular Mechanisms ◽  
Pyrin Domain ◽  
Human Lifespan ◽  
Age Related ◽  
Inflammatory State ◽  
Chronic Activation ◽  
Receptor Family

As a consequence of the considerable increase in the human lifespan over the last century, we are experiencing the appearance and impact of new age-related diseases. The causal relationships between aging and an enhanced susceptibility of suffering from a broad spectrum of diseases need to be better understood. However, one specific shared feature seems to be of capital relevance for most of these conditions: the low-grade chronic inflammatory state inherently associated with aging, i.e., inflammaging. Here, we review the molecular and cellular mechanisms that link aging and inflammaging, focusing on the role of the innate immunity and more concretely on the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, as well as how the chronic activation of this inflammasome has a detrimental effect on different age-related disorders.

New Insights about Regulatory T Cells Distribution and Function with Exercise: The Role of Immunometabolism

2020 ◽  
Vol 26 (9) ◽  
pp. 979-990 ◽  
Author(s):  
Gilson P. Dorneles ◽  
Aline A.Z. dos Passos ◽  
Pedro R.T. Romão ◽  
Alessandra Peres
Keyword(s):  
T Cells ◽  
Chronic Diseases ◽  
Experimental Studies ◽  
Treg Cells ◽  
Metabolic Phenotype ◽  
Acid Oxidation ◽  
Low Grade ◽  
And Function ◽  
Low Grade Inflammation

A lack of physical activity is linked to the development of many chronic diseases through a chronic low-grade inflammation state. It is now well accepted that the immune system plays a central role in the development of several chronic diseases, including insulin resistance, type 2 diabetes, atherosclerosis, heart failure and certain types of cancer. Exercise elicits a strong anti-inflammatory response independently of weight loss and can be a useful non-pharmacologic strategy to counteract the low-grade inflammation. The CD4+CD25+CD127- FoxP3+ Regulatory T (Treg) cells are a unique subset of helper T-cells, which regulate immune response and establish self-tolerance through the secretion of immunoregulatory cytokines, such as IL-10 and TGF-β, and the suppression of the function and activity of many immune effector cells (including monocytes/macrophages, dendritic cells, CD4+ and CD8+ T cells, and Natural Killers). The metabolic phenotype of Tregs are regulated by the transcription factor Foxp3, providing flexibility in fuel choice, but a preference for higher fatty acid oxidation. In this review, we focus on the mechanisms by which exercise - both acute and chronic - exerts its antiinflammatory effects through Treg cells mobilization. Furthermore, we discuss the implications of immunometabolic changes during exercise for the modulation of Treg phenotype and its immunosuppressive function. This narrative review focuses on the current knowledge regarding the role of Treg cells in the context of acute and chronic exercise using data from observational and experimental studies. Emerging evidence suggests that the immunomodulatory effects of exercise are mediated by the ability of exercise to adjust and improve Tregs number and function.

scholarly journals Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Michele Linsalata ◽  
Giuseppe Riezzo ◽  
Caterina Clemente ◽  
Benedetta D’Attoma ◽  
Francesco Russo
Keyword(s):  
Intestinal Barrier ◽  
Low Grade ◽  
Small Intestinal Mucosa ◽  
Gut Barrier Function ◽  
Inflammatory Bowel ◽  
Noninvasive Biomarkers ◽  
Irritable Bowel ◽  
And Function ◽  
Methodological Aspects ◽  
Low Grade Inflammation

The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.

scholarly journals Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 272
Author(s):  
Anna M. Fratta Pasini ◽  
Chiara Stranieri ◽  
Luciano Cominacini ◽  
Chiara Mozzini
Keyword(s):  
Potential Role ◽  
Viral Infections ◽  
Host Cells ◽  
Nuclear Factor ◽  
Angiotensin Converting Enzyme 2 ◽  
Pyrin Domain ◽  
Nrf2 Activation ◽  
Anti Inflammatory ◽  
Receptor Family

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

scholarly journals Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Maria Nardone ◽  
Roberto de Sire ◽  
Valentina Petito ◽  
Anna Testa ◽  
Guido Villani ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Adverse Outcomes ◽  
Low Grade ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Function ◽  
Host Metabolism ◽  
Low Grade Inflammation

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

scholarly journals NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiwen Zhang ◽  
Wenlin Yang ◽  
Wangen Li ◽  
Yunjuan Zhao
Keyword(s):  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Broad Spectrum ◽  
Nlrp3 Inflammasome ◽  
Main Function ◽  
Innate And Adaptive Immunity ◽  
Danger Signals ◽  
Pyrin Domain ◽  
Multimeric Protein ◽  
Receptor Family

Autoimmune diseases are a broad spectrum of human diseases that are characterized by the breakdown of immune tolerance and the production of autoantibodies. Recently, dysfunction of innate and adaptive immunity is considered to be a key step in the initiation and maintenance of autoimmune diseases. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex, which can detect exogenous pathogen irritants and endogenous danger signals. The main function of NLRP3 inflammasome is to promote secretion of interleukin (IL)-1β and IL-18, and pyroptosis mediated by caspase-1. Served as a checkpoint in innate and adaptive immunity, aberrant activation and regulation of NLRP3 inflammasome plays an important role in the pathogenesis of autoimmune diseases. This paper reviewed the roles of NLRP3 inflammasome in autoimmune diseases, which shows NLRP3 inflammasome may be a potential target for autoimmune diseases deserved further study.

scholarly journals Immune regulation of islet homeostasis and adaptation

2020 ◽  
Author(s):  
Jinglong Guo ◽  
Wenxian Fu
Keyword(s):  
Immune Cells ◽  
Cell Function ◽  
Normal Function ◽  
Low Grade ◽  
Multiple Organs ◽  
Monocytes And Macrophages ◽  
Β Cell Function ◽  
Islet Inflammation ◽  
And Function ◽  
Low Grade Inflammation

Abstract The islet of Langerhans produces endocrine hormones to regulate glucose homeostasis. The normal function of the islet relies on the homeostatic regulations of cellular composition and cell–cell interactions within the islet microenvironment. Immune cells populate the islet during embryonic development and participate in islet organogenesis and function. In obesity, a low-grade inflammation manifests in multiple organs, including pancreatic islets. Obesity-associated islet inflammation is evident in both animal models and humans, characterized by the accumulation of immune cells and elevated production of inflammatory cytokines/chemokines and metabolic mediators. Myeloid lineage cells (monocytes and macrophages) are the dominant types of immune cells in islet inflammation during the development of obesity and type 2 diabetes mellitus (T2DM). In this review, we will discuss the role of the immune system in islet homeostasis and inflammation and summarize recent findings of the cellular and molecular factors that alter islet microenvironment and β cell function in obesity and T2DM.

scholarly journals Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing

Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
Ginevra Nannelli ◽  
Marina Ziche ◽  
Sandra Donnini ◽  
Lucia Morbidelli
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Low Grade ◽  
Loss Of Function ◽  
Aldehyde Dehydrogenase 2 ◽  
Main Determinants ◽  
And Function ◽  
Low Grade Inflammation

Endothelial cells are the main determinants of vascular function, since their dysfunction in response to a series of cardiovascular risk factors is responsible for disease progression and further consequences. Endothelial dysfunction, if not resolved, further aggravates the oxidative status and vessel wall inflammation, thus igniting a vicious cycle. We have furthermore to consider the physiological manifestation of vascular dysfunction and chronic low-grade inflammation during ageing, also known as inflammageing. Based on these considerations, knowledge of the molecular mechanism(s) responsible for endothelial loss-of-function can be pivotal to identify novel targets of intervention with the aim of maintaining endothelial wellness and vessel trophism and function. In this review we have examined the role of the detoxifying enzyme aldehyde dehydrogenase 2 (ALDH2) in the maintenance of endothelial function. Its impairment indeed is associated with oxidative stress and ageing, and in the development of atherosclerosis and neurodegenerative diseases. Strategies to improve its expression and activity may be beneficial in these largely diffused disorders.

scholarly journals Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1565 ◽  
Author(s):  
Hedieh Keshavarz-Bahaghighat ◽  
Ahmed M. Darwesh ◽  
Deanna K. Sosnowski ◽  
John M. Seubert
Keyword(s):  
Heart Failure ◽  
Protective Role ◽  
Low Grade ◽  
Elderly Individuals ◽  
Cardiac Health ◽  
Age Related ◽  
And Function ◽  
Low Grade Inflammation ◽  
Insight Into ◽  
Increased Susceptibility

Age-associated changes leading to a decline in cardiac structure and function contribute to the increased susceptibility and incidence of cardiovascular diseases (CVD) in elderly individuals. Indeed, age is considered a risk factor for heart failure and serves as an important predictor for poor prognosis in elderly individuals. Effects stemming from chronic, low-grade inflammation, inflammaging, are considered important determinants in cardiac health; however, our understanding of the mechanisms involved remains unresolved. A steady decline in mitochondrial function is recognized as an important biological consequence found in the aging heart which contributes to the development of heart failure. Dysfunctional mitochondria contribute to increased cellular stress and an innate immune response by activating the NLRP-3 inflammasomes, which have a role in inflammaging and age-related CVD pathogenesis. Emerging evidence suggests a protective role for CYP450 epoxygenase metabolites of N-3 and N-6 polyunsaturated fatty acids (PUFA), epoxylipids, which modulate various aspects of the immune system and protect mitochondria. In this article, we provide insight into the potential roles N-3 and N-6 PUFA have modulating mitochondria, inflammaging and heart failure.

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