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Yi Liu, Bijaya Upadhyaya, Ali Reza Fardin-Kia, Robert M Juenemann, Moul Dey
Indigestible resistant starches (RS) are substrates for gut-microbial metabolism and have been shown to attenuate intestinal inflammation but the supporting evidence is inconsistent and lacks mechanistic explanation. We have recently reported dietary RS type 4 (RS4) induced improvements in immunometabolic functions in humans and a concomitant increase in butyrogenic gut-bacteria. Since inflammation is a key component in metabolic diseases, here we investigated the effects of RS4-derived butyrate on the epigenetic repression of pro-inflammatory genes in vivo and in vitro...
September 14, 2016: Food & Function
Kevin Man, Vassily I Kutyavin, Ajay Chawla
Evolution of metazoans resulted in the specialization of cellular and tissue function. This was accomplished by division of labor, which allowed tissue parenchymal cells to prioritize their core functions while ancillary functions were delegated to tissue accessory cells, such as immune, stromal, and endothelial cells. In metabolic organs, the accessory cells communicate with their clients, the tissue parenchymal cells, to optimize cellular processes, allowing organisms to adapt to changes in their environment...
September 21, 2016: Cell Metabolism
Rob J W Arts, Leo A B Joosten, Mihai G Netea
The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes...
September 26, 2016: Seminars in Immunology
Kae Won Cho, Brian F Zamarron, Lindsey A Muir, Kanakadurga Singer, Cara E Porsche, Jennifer B DelProposto, Lynn Geletka, Kevin A Meyer, Robert W O'Rourke, Carey N Lumeng
Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Elisabeth Kugelberg
No abstract text is available yet for this article.
September 27, 2016: Nature Reviews. Immunology
Shuai Jiang, Wei Yan
T cells play critical roles in host defenses against cancer. External signals prompt activation of naïve T cells, triggering modulation of their immune functions. Emerging evidence reveals that distinct metabolic changes impact the immune functions of naïve and effector T cells, including CD4(+) and CD8(+) T cells. Since T cells appear to be key players in tumor progression, it is important to elucidate whether and how T-cell metabolic reprogramming might alter their impact on cancer progression. Here we briefly review the available knowledge regarding T cells in relation to cancer, focusing on the metabolic reprogramming of T cells and how this influences tumor progression...
September 21, 2016: Cancer Letters
Harding H Luan, Ruslan Medzhitov
Itaconate is a newly discovered mammalian metabolite bearing significant implications for our understanding of cellular immunometabolism and antimicrobial defense. Here, we explore recent findings regarding the role of itaconate in the innate immune response and highlight the emerging principle that metabolites can have distinct immunological functions independent of bioenergetics.
September 13, 2016: Cell Metabolism
Z Zhou, O Bulgari, M Vailati-Riboni, E Trevisi, M A Ballou, F C Cardoso, D N Luchini, J J Loor
The immunometabolic status of peripartal cows is altered due to changes in liver function, inflammation, and oxidative stress. Nutritional management during this physiological state can affect the biological components of immunometabolism. The objectives of this study were to measure concentrations of biomarkers in plasma, liver tissue, and milk, and also polymorphonuclear leukocyte function to assess the immunometabolic status of cows supplemented with rumen-protected methionine (MET) or choline (CHOL). Forty-eight multiparous Holstein cows were used in a randomized complete block design with 2 × 2 factorial arrangement of MET (Smartamine M, Adisseo NA) and CHOL (ReaShure, Balchem Inc...
August 31, 2016: Journal of Dairy Science
Jason Gardner
A new type of medicine was approved in Europe at the end of May that culminated from the successful convergence of two fields of science: stem cell transplantation and gene therapy. Strimvelis, a patient-specific gene-modified stem cell medicine for ADA-SCID (a fatal immunometabolic disorder similar to the bubble-boy disease), was developed by scientists at the San Raffaele Telethon Institute for Gene Therapy (TIGET) in Milan, then later partnered with GSK. The journey took over 25 years of dedicated work from many groups and involved a pivotal trial with 12 children and their brave families...
August 30, 2016: Human Gene Therapy. Clinical Development
Hui Jiang, Hengfei Shi, Man Sun, Yafeng Wang, Qingzhou Meng, Panpan Guo, Yanlan Cao, Jiong Chen, Xiang Gao, Erguang Li, Jianghuai Liu
Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3)...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jenny Freitag, Luciana Berod, Thomas Kamradt, Tim Sparwasser
A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity...
October 11, 2016: Immunology and Cell Biology
X-J Xia, Y-Y Gao, J Zhang, L Wang, S Zhao, Y-Y Che, C-J Ao, H-J Yang, J-Q Wang, L-C Lei
Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-γ has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-γ can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-γ treatment, autophagy and malignant transformation and of the mechanism underlying IFN-γ-induced autophagy and subsequent malignant transformation in primary BMECs...
2016: Cell Death Discovery
Neetu Srivastava, Sonia Iyer, Raki Sudan, Christie Youngs, Robert W Engelman, Kyle T Howard, Christopher M Russo, John D Chisholm, William G Kerr
Low-grade chronic inflammation is a key etiological phenomenon responsible for the initiation and perpetuation of obesity and diabetes. Novel therapeutic approaches that can specifically target inflammatory pathways are needed to avert this looming epidemic of metabolic disorders. Genetic and chemical inhibition of SH2-containing inositol 5' phosphatase 1 (SHIP1) has been associated with systemic expansion of immunoregulatory cells that promote a lean-body state; however, SHIP1 function in immunometabolism has never been assessed...
July 21, 2016: JCI Insight
Nicole G Grün, Karina Zeyda, Veronica Moreno-Viedma, Karin Strohmeier, Günther Staffler, Maximilian Zeyda, Thomas M Stulnig
Osteopontin (OPN) is a multifunctional protein involved in several inflammatory processes and pathogeneses including obesity-related disorders and cancer. OPN binds to a variety of integrin receptors and CD44 resulting in a proinflammatory stimulus. Therefore, OPN constitutes a novel interesting target to develop new therapeutic strategies, which counteract OPN's proinflammatory properties. We established a humanized SPP1 (hSPP1) mouse model and evaluated its suitability as a model for obesity and insulin resistance...
July 18, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Wei Li, Ramya Sivakumar, Anton A Titov, Seung-Chul Choi, Laurence Morel
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism...
2016: Critical Reviews in Immunology
M Zaeem Cader, Katharina Boroviak, Qifeng Zhang, Ghazaleh Assadi, Sarah L Kempster, Gavin W Sewell, Svetlana Saveljeva, Jonathan W Ashcroft, Simon Clare, Subhankar Mukhopadhyay, Karen P Brown, Markus Tschurtschenthaler, Tim Raine, Brendan Doe, Edwin R Chilvers, Jules L Griffin, Nicole C Kaneider, R Andres Floto, Mauro D'Amato, Allan Bradley, Michael J O Wakelam, Gordon Dougan, Arthur Kaser
Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration...
September 2016: Nature Immunology
Maddalena Coppo, Yurii Chinenov, Maria A Sacta, Inez Rogatsky
Diet-induced obesity causes chronic macrophage-driven inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT macrophages, however, differ in their origin, gene expression and activities: unlike infiltrating monocyte-derived inflammatory macrophages, WAT-resident macrophages counteract inflammation and insulin resistance, yet, the mechanisms underlying their transcriptional programming remain poorly understood. We recently reported that a nuclear receptor cofactor-glucocorticoid receptor (GR)-interacting protein (GRIP)1-cooperates with GR to repress inflammatory genes...
2016: Nature Communications
Fazlin Mohd Fauzi, Cini Mathew John, Arunkumar Karunanidhi, Hamse Y Mussa, Rajesh Ramasamy, Aishah Adam, Andreas Bender
ETHNOPHARMACOLOGICAL RELEVANCE: Cassia auriculata (CA) is used as an antidiabetic therapy in Ayurvedic and Siddha practice. This study aimed to understand the mode-of-action of CA via combined cheminformatics and in vivo biological analysis. In particular, the effect of 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied. MATERIALS AND METHODS: In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations...
July 21, 2016: Journal of Ethnopharmacology
Nicholas J Matheson, Edward Jd Greenwood, Paul J Lehner
Evolutionary pressure has produced an 'arms race' between cellular restriction factors (limiting viral replication) and viral proteins (overcoming host restriction). The host factors SAMHD1 and SLFN1 patrol metabolic bottlenecks required for HIV replication. Conversely, the HIV accessory proteins Vpx, Vpu and Nef manipulate cellular metabolism to enable viral replication. Recent work identifying Vpu-mediated downregulation of the alanine transporter SNAT1 and Nef-mediated downregulation of the serine carriers SERINC3/5 has uncovered the importance of HIV manipulation of the amino acid supply...
August 2016: Current Opinion in Virology
Sukanya Raghuraman, Ida Donkin, Soetkin Versteyhe, Romain Barrès, David Simar
Recent research developments have shed light on the risk factors contributing to metabolic complications, implicating both genetic and environmental factors, potentially integrated by epigenetic mechanisms. Distinct epigenetic changes in immune cells are frequently observed in obesity and type 2 diabetes mellitus, and these are associated with alterations in the phenotype, function, and trafficking patterns of these cells. The first step in the development of effective therapeutic strategies is the identification of distinct epigenetic signatures associated with metabolic disorders...
July 18, 2016: Trends in Endocrinology and Metabolism: TEM
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