Tissue factor pathways linking obesity and inflammation. 2015

W Ruf, and F Samad
Wolfram Ruf, M.D., Professor, Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, Mail stop: SP258, Tel. 858/784-2748, Fax -8480, E-mail: ruf@uni-mainz.de, ruf@scripps.edu.

Obesity is a major cause for a spectrum of metabolic syndrome-related diseases that include insulin resistance, type 2 diabetes, and steatosis of the liver. Inflammation elicited by macrophages and other immune cells contributes to the metabolic abnormalities in obesity. In addition, coagulation activation following tissue factor (TF) upregulation in adipose tissue is frequently found in obese patients and particularly associated with diabetic complications. Genetic and pharmacological evidence indicates that TF makes significant contributions to the development of the metabolic syndrome by signaling through G protein-coupled protease activated receptors (PARs). Adipocyte TF-PAR2 signaling contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas hematopoietic TF-PAR2 signaling is a major cause for adipose tissue inflammation, hepatic steatosis and inflammation, as well as insulin resistance. In the liver of mice on a high fat diet, PAR2 signaling increases transcripts of key regulators of gluconeogenesis, lipogenesis and inflammatory cytokines. Increased markers of hepatic gluconeogenesis correlate with decreased activation of AMP-activated protein kinase (AMPK), a known regulator of these pathways and a target for PAR2 signaling. Clinical markers of a TF-induced prothrombotic state may thus indicate a risk in obese patient for developing complications of the metabolic syndrome.

UI MeSH Term Description Entries
D007155 Immunologic Factors Biologically active substances whose activities affect or play a role in the functioning of the immune system. Biological Response Modifier,Biomodulator,Immune Factor,Immunological Factor,Immunomodulator,Immunomodulators,Biological Response Modifiers,Biomodulators,Factors, Immunologic,Immune Factors,Immunological Factors,Modifiers, Biological Response,Response Modifiers, Biological,Factor, Immune,Factor, Immunological,Factors, Immune,Factors, Immunological,Modifier, Biological Response,Response Modifier, Biological
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013925 Thromboplastin Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. Antigens, CD142,CD142 Antigens,Coagulation Factor III,Factor III,Tissue Factor,Tissue Thromboplastin,Blood Coagulation Factor III,Coagulin,Glomerular Procoagulant Activity,Prothrombinase,Tissue Factor Procoagulant,Urothromboplastin,Activity, Glomerular Procoagulant,Factor III, Coagulation,Procoagulant Activity, Glomerular,Procoagulant, Tissue Factor,Thromboplastin, Tissue
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D044464 Receptor, PAR-2 A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence. PAR-2 Receptor,Proteinase Activated Receptor 2,PAR2 Receptor,Protease-Activated Receptor 2,Receptor, Trypsin,Trypsin Receptor,Trypsin Receptors,PAR 2 Receptor,Protease Activated Receptor 2,Receptor 2, Protease-Activated,Receptor, PAR 2,Receptor, PAR2,Receptors, Trypsin
D018448 Models, Immunological Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment. Immunological Models,Immunologic Model,Model, Immunologic,Immunologic Models,Immunological Model,Model, Immunological,Models, Immunologic
D024821 Metabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. Cardiometabolic Syndrome,Insulin Resistance Syndrome X,Metabolic Syndrome X,Reaven Syndrome X,Dysmetabolic Syndrome X,Metabolic Cardiovascular Syndrome,Metabolic X Syndrome,Syndrome X, Insulin Resistance,Syndrome X, Metabolic,Cardiometabolic Syndromes,Cardiovascular Syndrome, Metabolic,Cardiovascular Syndromes, Metabolic,Metabolic Syndromes,Syndrome X, Dysmetabolic,Syndrome X, Reaven,Syndrome, Cardiometabolic,Syndrome, Metabolic,Syndrome, Metabolic Cardiovascular,Syndrome, Metabolic X,Syndromes, Cardiometabolic,Syndromes, Metabolic,X Syndrome, Metabolic

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