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Macrophage metabolism

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https://www.readbyqxmd.com/read/28817438/alternatively-activated-macrophages-drive-browning-of-white-adipose-tissue-in-burns
#1
Abdikarim Abdullahi, Christopher Auger, Mile Stanojcic, David Patsouris, Alexandra Parousis, Slava Epelman, Marc G Jeschke
OBJECTIVE: The aim of this study was to uncover the mediators and mechanistic events that facilitate the browning of white adipose tissue (WAT) in response to burns. BACKGROUND: In hypermetabolic patients (eg, burns, cancer), the browning of WAT has presented substantial clinical challenges related to cachexia, atherosclerosis, and poor clinical outcomes. Browning of the adipose tissue has recently been found to induce and sustain hypermetabolism. Although browning appears central in trauma-, burn-, or cancer-induced hypermetabolic catabolism, the mediators are essentially unknown...
August 16, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#2
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813479/metabolomic-profiling-of-amines-in-sepsis-predicts-changes-in-nos-canonical-pathways
#3
Abel Tesfai, Niall MacCallum, Nicholas S Kirkby, Hime Gashaw, Nicola Gray, Elizabeth Want, Gregory J Quinlan, Sharon Mumby, James M Leiper, Mark Paul-Clark, Blerina Ahmetaj-Shala, Jane A Mitchell
RATIONALE: Nitric oxide synthase (NOS) is a biomarker/target in sepsis. NOS activity is driven by amino acids, which cycle to regulate the substrate L-arginine in parallel with cycles which regulate the endogenous inhibitors ADMA and L-NMMA. The relationship between amines and the consequence of plasma changes on iNOS activity in early sepsis is not known. OBJECTIVE: Our objective was to apply a metabolomics approach to determine the influence of sepsis on a full array of amines and what consequence these changes may have on predicted iNOS activity...
2017: PloS One
https://www.readbyqxmd.com/read/28812211/the-immune-system-in-obesity-developing-paradigms-amidst-inconvenient-truths
#4
REVIEW
Madhur Agrawal, Philip A Kern, Barbara S Nikolajczyk
PURPOSE OF REVIEW: Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. RECENT FINDINGS: Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28810589/phenotypic-switch-in-lung-interstitial-macrophage-polarization-in-an-ovalbumin-induced-mouse-model-of-asthma
#5
Hanxiang Nie, Ailing Wang, Qing He, Qiaoyu Yang, Linlin Liu, Guqin Zhang, Yi Huang, Xuhong Ding, Hongying Yu, Suping Hu
Macrophage phenotype and function varies according to their polarized state, which in turn is dependent on microenvironmental stimuli. Under normal physiological conditions, lung interstitial macrophages that express interleukin (IL)-10 are considered to serve regulatory roles in the prevention of allergic reactions in the airways. However, the phenotypic profile of lung interstitial macrophages during the pathophysiology of asthma remains unknown. In the current study, the phenotypic characteristics of lung interstitial macrophages were investigated in an ovalbumin (OVA)-induced mouse model of asthma...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808185/establishment-of-a-rat-model-with-diet-induced-coronary-atherosclerosis
#6
Mingming Gao, Guo Xin, Xu Qiu, Yuhui Wang, George Liu
Coronary atherosclerotic disease is a serious disease in humans, but no suitable animal model is available currently for further studies. We used apolipoprotein E gene knockout (ApoE KO) rats to induce hypercholesterolemia through a special high cholesterol/bile salt diet (Paigen diet), then analyzed aortic and coronary atherosclerosis lesions and the myocardial injury in order to establish a novel small animal model of coronary atherosclerosis. Plasma cholesterol of ApoE KO rats increased 7.6-fold compared with wild-type rats after 8 weeks on the Paigen diet...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808162/listeria-monocytogenes-and-shigella-flexneri-activate-the-nlrp1b-inflammasome
#7
Jana Neiman-Zenevich, Sarah Stuart, Mena Abdel-Nour, Stephen E Girardin, Jeremy Mogridge
Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might, therefore, sense microbial infection as intracellular pathogens such as Listeria monocytogenes and Shigella flexneri cause metabolic stress as a result of nutrient scavenging and host cell damage...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28807612/the-role-of-trimethylamine-n-oxide-as-a-mediator-of-cardiovascular-complications-in-chronic-kidney-disease
#8
James A P Tomlinson, David C Wheeler
Patients with chronic kidney disease (CKD) have an enhanced risk of cardiovascular (CV) morbidity and mortality when compared with age- and gender-matched individuals with normal kidney function. Trimethlyamine N-oxide (TMAO) is a gut-derived amine oxide that has been implicated in the causation of CV diseases. Plasma TMAO is cleared by the kidney, and TMAO levels are elevated in CKD. Experimental studies have identified pathogenic mechanisms by which TMAO may contribute to CV disease through dysregulation of lipid metabolism, enhanced macrophage foam cell formation, and platelet dysfunction...
August 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28806468/an-overview-of-hemophagocytic-lymphohistiocytosis
#9
Ysabella M Esteban, Jill L O de Jong, Melissa S Tesher
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by a dysregulated hyperinflammatory response associated with aberrant activation of lymphocytes and macrophages that results in hypercytokinemia. It is classically divided into two types: (1) primary or familial HLH and (2) secondary HLH. Familial HLH is generally an autosomal recessive condition, whereas secondary HLH is usually associated with infectious diseases, autoinflammatory and autoimmune diseases (where it is more commonly known as macrophage activation syndrome), malignancy, immunosuppression, hematopoietic stem cell transplantation, organ transplantation, HIV infection, and metabolic diseases...
August 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/28806274/transfusion-related-immunomodulation-a-reappraisal
#10
Lyla A Youssef, Steven L Spitalnik
PURPOSE OF REVIEW: This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing 'pure' red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the 'storage lesion...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28805975/antofine-suppresses-endotoxin-induced-inflammation-and-metabolic-disorder-via-amp-activated-protein-kinase
#11
Shao-Ting Chou, Fang Jung, Shih-Hsing Yang, Hwei-Ling Chou, Guey-Mei Jow, Jau-Chen Lin
The inhibition of activated macrophages has been used to develop anti-inflammatory agents for therapeutic intervention to human diseases that cause excessive inflammatory responses. Antofine, a phenanthroindolizidine alkaloid, has a potent anti-inflammatory effect. However, the molecular mechanisms of its anti-inflammatory activity have not yet been fully detailed. In this study, we comprehensively explored the anti-inflammatory effects of antofine on endotoxin-induced inflammation in macrophages using cDNA microarray analysis, thereby elucidating the potential mechanism by which antofine suppresses inflammation...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804459/metabolic-variability-of-a-multispecies-probiotic-preparation-impacts-on-the-anti-inflammatory-activity
#12
Michele Biagioli, Luca Laghi, Adriana Carino, Sabrina Cipriani, Eleonora Distrutti, Silvia Marchianò, Carola Parolin, Paolo Scarpelli, Beatrice Vitali, Stefano Fiorucci
Background: In addition to strain taxonomy, the ability of probiotics to confer beneficial effects on the host rely on a number of additional factors including epigenetic modulation of bacterial genes leading to metabolic variability and might impact on probiotic functionality. Aims: To investigate metabolism and functionality of two different batches of a probiotic blend commercialized under the same name in Europe in models of intestinal inflammation. Methods: Boxes of VSL#3, a probiotic mixture used in the treatment of pouchitis, were obtained from pharmacies in UK subjected to metabolomic analysis and their functionality tested in mice rendered colitis by treatment with DSS or TNBS...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28802038/trem2-maintains-microglial-metabolic-fitness-in-alzheimer-s-disease
#13
Tyler K Ulland, Wilbur M Song, Stanley Ching-Cheng Huang, Jason D Ulrich, Alexey Sergushichev, Wandy L Beatty, Alexander A Loboda, Yingyue Zhou, Nigel J Cairns, Amal Kambal, Ekaterina Loginicheva, Susan Gilfillan, Marina Cella, Herbert W Virgin, Emil R Unanue, Yaming Wang, Maxim N Artyomov, David M Holtzman, Marco Colonna
Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28801262/the-physiological-and-pathophysiological-roles-of-taurine-in-adipose-tissue-in-relation-to-obesity
#14
REVIEW
Shigeru Murakami
Obesity is caused by an imbalance between energy intake and energy expenditure. It is established that obesity is a state of low-grade chronic inflammation, which is characterized by enlarged hypertrophied adipocytes, increased infiltration by macrophages and marked changes in the secretion of adipokines and free fatty acids. The effects of taurine on the pathogenesis of obesity have been reported in animals and humans. Although the mechanisms underlying the anti-obesity action of taurine remain to be defined, taurine seems to ameliorate obesity through stimulation of energy expenditure, modulation of lipid metabolism, anorexic effect, anti-inflammatory and anti-oxidative effects...
August 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28801231/anti-inflammatory-chromatinscape-suggests-alternative-mechanisms-of-glucocorticoid-receptor-action
#15
Kyu-Seon Oh, Heta Patel, Rachel A Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D C Fraser, Gordon L Hager, Myong-Hee Sung
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS)...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28798743/l-arginine-uptake-by-cationic-amino-acid-transporter-promotes-intra-macrophage-survival-of-leishmania-donovani-by-enhancing-arginase-mediated-polyamine-synthesis
#16
Abhishek Mandal, Sushmita Das, Ajay Kumar, Saptarshi Roy, Sudha Verma, Ayan Kumar Ghosh, Ruby Singh, Kumar Abhishek, Savita Saini, Abul Hasan Sardar, Bidyut Purkait, Ashish Kumar, Chitra Mandal, Pradeep Das
The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL), depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM) with Leishmania, resulted in upregulation of l-arginine transport...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28798256/metabolic-characterization-and-rna-profiling-reveal-glycolytic-dependence-of-pro-fibrotic-phenotype-of-alveolar-macrophages-in-lung-fibrosis
#17
Na Xie, Huachun Cui, Jing Ge, Sami Banerjee, Sijia Guo, Shubham Dubey, Edward Abraham, Rui-Ming Liu, Gang Liu
Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798202/aerobic-exercise-elevates-markers-of-angiogenesis-and-macrophage-il6-gene-expression-in-the-subcutaneous-adipose-tissue-of-overweight-to-obese-adults
#18
Douglas W Van Pelt, Lisa M Guth, Jeffrey F Horowitz
Alterations in the inflammatory state, metabolic function, and structure of subcutaneous adipose tissue (SAT) can impact the development of insulin resistance in obesity. Exercise can improve metabolic health in obesity, but the effects of exercise on SAT are not well known. The purpose of this study was to examine the effects of acute exercise and habitual exercise training on mRNA expression of markers of lipid metabolism, inflammation, fibrosis, and hypoxia/angiogenesis in SAT, as well as adipocyte cell size...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28798141/characterization-of-macrophage-polarization-states-using-combined-measurement-of-2-deoxyglucose-and-glutamine-accumulation-implications-for-imaging-of-atherosclerosis
#19
Sina Tavakoli, Kevin Downs, John D Short, Huynh Nga Nguyen, Yanlai Lai, Paul A Jerabek, Beth Goins, Jakub Toczek, Mehran M Sadeghi, Reto Asmis
OBJECTIVE: Despite the early promising results of (18)F-fluorodeoxyglucose positron emission tomography for assessment of vessel wall inflammation, its accuracy in prospective identification of vulnerable plaques has remained limited. Additionally, previous studies have indicated that (18)F-fluorodeoxyglucose uptake alone may not allow for accurate identification of specific macrophage activation states. We aimed to determine whether combined measurement of glucose and glutamine accumulation-the 2 most important bioenergetic substrates for macrophages-improves the distinction of macrophage inflammatory states and can be utilized to image atherosclerosis...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28798047/mtor-regulates-metabolic-adaptation-of-apcs-in-the-lung-and-controls-the-outcome-of-allergic-inflammation
#20
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity...
August 10, 2017: Science
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