scholarly journals Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

2018 ◽  
Vol 19 (10) ◽  
pp. 3092 ◽  
Author(s):  
Claire Lyons ◽  
Helen Roche
Keyword(s):  
Immune Cell ◽  
Cell Metabolism ◽  
Nutrient Status ◽  
Whole Body ◽  
Direct Role ◽  
Insulin Metabolism ◽  
Metabolic Inflammation ◽  
Metabolic Substrates ◽  
Whole Body Metabolism ◽  
And Function

Nutritional status provides metabolic substrates to activate AMP-Activated Protein Kinase (AMPK), the energy sensor that regulates metabolism. Recent evidence has demonstrated that AMPK has wider functions with respect to regulating immune cell metabolism and function. One such example is the regulatory role that AMPK has on NLRP3-inlflammasome and IL-1β biology. This in turn can result in subsequent negative downstream effects on glucose, lipid and insulin metabolism. Nutrient stress in the form of obesity can impact AMPK and whole-body metabolism, leading to complications such as type 2 diabetes and cancer risk. There is a lack of data regarding the nature and extent that nutrient status has on AMPK and metabolic-inflammation. However, emerging work elucidates to a direct role of individual nutrients on AMPK and metabolic-inflammation, as a possible means of modulating AMPK activity. The posit being to use such nutritional agents to re-configure metabolic-inflammation towards more oxidative phosphorylation and promote the resolution of inflammation. The complex paradigm will be discussed within the context of if/how dietary components, nutrients including fatty acids and non-nutrient food components, such as resveratrol, berberine, curcumin and the flavonoid genistein, modulate AMPK dependent processes relating to inflammation and metabolism.

scholarly journals Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Felix Clemens Richter ◽  
Aljawharah Alrubayyi ◽  
Alicia Teijeira Crespo ◽  
Sarah Hulin-Curtis ◽  
Keyword(s):  
Lipid Metabolism ◽  
Influenza A ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Low Grade ◽  
Obese Patients ◽  
Healthy Weight ◽  
Virus Infections ◽  
Immune Alterations ◽  
And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

scholarly journals OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance

2020 ◽  
Vol 117 (28) ◽  
pp. 16616-16625
Author(s):  
Yunfan Yang ◽  
Xiruo Li ◽  
Harding H. Luan ◽  
Bichen Zhang ◽  
Kaisi Zhang ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Nutrient Sensing ◽  
Metabolic Disturbance ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Peripheral Tissues ◽  
Mtorc1 Signaling ◽  
Whole Body Metabolism ◽  
Glcnac Transferase

Enhanced inflammation is believed to contribute to overnutrition-induced metabolic disturbance. Nutrient flux has also been shown to be essential for immune cell activation. Here, we report an unexpected role of nutrient-sensingO-linked β-N-acetylglucosamine (O-GlcNAc) signaling in suppressing macrophage proinflammatory activation and preventing diet-induced metabolic dysfunction. Overnutrition stimulates an increase inO-GlcNAc signaling in macrophages.O-GlcNAc signaling is down-regulated during macrophage proinflammatory activation. SuppressingO-GlcNAc signaling byO-GlcNAc transferase (OGT) knockout enhances macrophage proinflammatory polarization, promotes adipose tissue inflammation and lipolysis, increases lipid accumulation in peripheral tissues, and exacerbates tissue-specific and whole-body insulin resistance in high-fat-diet-induced obese mice. OGT inhibits macrophage proinflammatory activation by catalyzing ribosomal protein S6 kinase beta-1 (S6K1)O-GlcNAcylation and suppressing S6K1 phosphorylation and mTORC1 signaling. These findings thus identify macrophageO-GlcNAc signaling as a homeostatic mechanism maintaining whole-body metabolism under overnutrition.

Mitochondrial form, function and signalling in aging

2016 ◽  
Vol 473 (20) ◽  
pp. 3421-3449 ◽  
Author(s):  
Ignacio Amigo ◽  
Fernanda M. da Cunha ◽  
Maria Fernanda Forni ◽  
Wilson Garcia-Neto ◽  
Pâmela A. Kakimoto ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Energy Homeostasis ◽  
Cell Types ◽  
Redox Balance ◽  
Whole Body ◽  
Model Organisms ◽  
Resistance To Stress ◽  
Whole Body Metabolism ◽  
And Function ◽  
Different Characteristics

Aging is often accompanied by a decline in mitochondrial mass and function in different tissues. Additionally, cell resistance to stress is frequently found to be prevented by higher mitochondrial respiratory capacity. These correlations strongly suggest mitochondria are key players in aging and senescence, acting by regulating energy homeostasis, redox balance and signalling pathways central in these processes. However, mitochondria display a wide array of functions and signalling properties, and the roles of these different characteristics are still widely unexplored. Furthermore, differences in mitochondrial properties and responses between tissues and cell types, and how these affect whole body metabolism are also still poorly understood. This review uncovers aspects of mitochondrial biology that have an impact upon aging in model organisms and selected mammalian cells and tissues.

scholarly journals Changes in Nutritional Status Impact Immune Cell Metabolism and Function

2018 ◽  
Vol 9 ◽  
Author(s):  
Yazan Alwarawrah ◽  
Kaitlin Kiernan ◽  
Nancie J. MacIver
Keyword(s):  
Nutritional Status ◽  
Immune Cell ◽  
Cell Metabolism ◽  
And Function

scholarly journals Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Javier Traba ◽  
Michael N. Sack ◽  
Thomas A. Waldmann ◽  
Olga M. Anton
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Immune Surveillance ◽  
Antitumor Effects ◽  
Cancer Management ◽  
Immunosuppressive Tumor Microenvironment ◽  
And Function ◽  
Main Effects

Constitutive activity of the immune surveillance system detects and kills cancerous cells, although many cancers have developed strategies to avoid detection and to resist their destruction. Cancer immunotherapy entails the manipulation of components of the endogenous immune system as targeted approaches to control and destroy cancer cells. Since one of the major limitations for the antitumor activity of immune cells is the immunosuppressive tumor microenvironment (TME), boosting the immune system to overcome the inhibition provided by the TME is a critical component of oncotherapeutics. In this article, we discuss the main effects of the TME on the metabolism and function of immune cells, and review emerging strategies to potentiate immune cell metabolism to promote antitumor effects either as monotherapeutics or in combination with conventional chemotherapy to optimize cancer management.

scholarly journals Rational Design and In Vivo Characterization of Vaccine Adjuvants

ILAR Journal ◽  
2018 ◽  
Vol 59 (3) ◽  
pp. 309-322
Author(s):  
Signe Tandrup Schmidt ◽  
Gabriel Kristian Pedersen ◽  
Dennis Christensen
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Rational Design ◽  
Immune Cell ◽  
Whole Body ◽  
Target Antigen ◽  
Vaccine Adjuvants ◽  
Human Situation ◽  
And Function

Abstract Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used. In this review, we present methods for assessing adjuvant efficacy and function in animal models: (1) whole-body biodistribution evaluated by using fluorescently and radioactively labeled vaccine components; (2) association and activation of immune cell subsets at the injection site, in the draining lymph node, and the spleen; (4) adaptive immune responses, such as cytotoxic T-lymphocytes, various T-helper cell subsets, and antibody responses, which may be quantitatively evaluated using ELISA, ELISPOT, and immunoplex assays and qualitatively evaluated using flow cytometric and single cell sequencing assays; and (5) effector responses, for example, antigen-specific cytotoxic potential of CD8+ T cells and antibody neutralization assays. While the vaccine-induced immune responses in mice often correlate with the responses induced in humans, there are instances where immune responses detected in mice are not translated to the human situation. We discuss some examples of correlation and discrepancy between mouse and human immune responses and how to understand them.

scholarly journals Parenteral glucose supply and pharmacological glycolysis inhibition determine the clinical fate of infected preterm newborns

2021 ◽  
Author(s):  
Tik Muk ◽  
Anders Brunse ◽  
Nicole L Henriksen ◽  
Karoline Aasmul-Olsen ◽  
Duc Ninh Nguyen
Keyword(s):  
Preterm Infants ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Preterm Neonates ◽  
Glucose Levels ◽  
Lactate Acidosis ◽  
Infection Response ◽  
Host Infection ◽  
And Function ◽  
Glucose Supply

Preterm infants are susceptible to bloodstream infection that can lead to sepsis. High parenteral glucose supplement is commonly used to support their growth and energy expenditure, but may exceed endogenous regulation during infection, causing dysregulated immune response and clinical deterioration. Using a preterm piglet model of neonatal sepsis induced by Staphylococcus epidermidis infection, we demonstrate the delicate interplay between immunity and energy metabolism to regulate the host infection response. Circulating glucose levels, glycolysis and inflammatory response to infection are closely connected across the states of tolerance, resistance and immunoparalysis. Further, high parenteral glucose provision during infection induces hyperglycemia, elevated glycolysis and inflammation, leading to lactate acidosis and sepsis, whereas glucose restricted individuals are clinically unaffected with increased gluconeogenesis to maintain moderate hypoglycemia. Finally, pharmacological glycolysis inhibition during normoglycemia enhances bacterial clearance and dampens inflammation but fails to prevent sepsis. Our results uncover how blood glucose controls immune cell metabolism and function, in turn determining the clinical fate of infected preterm neonates. This also questions the current practice of parenteral glucose supply for infected preterm infants.

scholarly journals Bone-Derived Modulators That Regulate Brain Function: Emerging Therapeutic Targets for Neurological Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongzhen Chen ◽  
Dewei Shang ◽  
Yuguan Wen ◽  
Chao Liang
Keyword(s):  
Stem Cells ◽  
Neurological Disorders ◽  
Brain Function ◽  
The Body ◽  
Whole Body ◽  
Lipocalin 2 ◽  
Hematopoietic Stem ◽  
Bone Marrow Derived Cells ◽  
Whole Body Metabolism ◽  
And Function

Bone has traditionally been regarded as a structural organ that supports and protects the various organs of the body. Recent studies suggest that bone also acts as an endocrine organ to regulate whole-body metabolism. Particularly, homeostasis of the bone is shown to be necessary for brain development and function. Abnormal bone metabolism is associated with the onset and progression of neurological disorders. Recently, multiple bone-derived modulators have been shown to participate in brain function and neurological disorders, including osteocalcin, lipocalin 2, and osteopontin, as have bone marrow-derived cells such as mesenchymal stem cells, hematopoietic stem cells, and microglia-like cells. This review summarizes current findings regarding the roles of these bone-derived modulators in the brain, and also follows their involvement in the pathogenesis of neurological disorders. The content of this review may aide in the development of promising therapeutic strategies for neurological disorders via targeting bone.

scholarly journals Is nuclear sirtuin SIRT6 a master regulator of immune function?

2020 ◽  
Author(s):  
Vinodkumar B Pillai ◽  
Mahesh P Gupta
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Warburg Effect ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Negative Regulator ◽  
Master Regulator ◽  
Energy Needs ◽  
And Function ◽  
The Warburg Effect

Abstract: The ability to ward off pathogens with minimal damage to the host determines the immune system's robustness. Multiple factors, including pathogen processing, identification, secretion of mediator and effector molecules, and immune cell proliferation and differentiation into various subsets, constitute the success of mounting an effective immune response. Cellular metabolism controls all of these intricate processes. Cells utilize diverse fuel sources and switch back and forth between different metabolic pathways depending on their energy needs. The three most critical metabolic pathways on which immune cells depend to meet their energy needs are oxidative metabolism, glycolysis, and glutaminolysis. Dynamic switching between these metabolic pathways is needed for optimal function of the immune cells. Moreover, switching between these metabolic pathways needs to be tightly regulated to achieve the best results. Immune cells depend on the Warburg effect for their growth, proliferation, secretory, and effector functions. Here, we hypothesize that the sirtuin, SIRT6, could be a negative regulator of the Warburg effect. We also postulate that SIRT6 could act as a master regulator of immune cell metabolism and function by regulating critical signaling pathways.

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