interleukin-8 and Obesity

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

Topics: Adipokines; Cardiovascular Diseases; COVID-19; Cytokines; Diabetes Mellitus, Type 2; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Obesity; Pandemics; RNA, Viral; SARS-CoV-2

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 β, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.

Topics: Adipose Tissue; Chemokine CCL2; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Lipopolysaccharides; Macrophages; Monocytes; Neoplasms; Obesity; Tumor Necrosis Factor-alpha

Skeletal muscle and adipose tissue are the two largest organs in the body. Skeletal muscle is an effector organ, and adipose tissue is an organ that stores energy; in addition, they are endocrine organs that secrete cytokines, namely myokines and adipokines, respectively. Myokines consist of myostatin, interleukin (IL)-8, IL-15, irisin, fibroblast growth factor 21, and myonectin; adipokines include leptin, adiponectin, resistin, chemerin, and visfatin. Furthermore, certain cytokines, such as IL-6 and tumor necrosis factor-α, are released by both skeletal muscle and adipose tissue and exhibit a bioactive effect; thus, they are called adipo-myokines. Recently, novel myokines or adipokines were identified through the secretomic technique, which has expanded our knowledge on the previously unknown functions of skeletal muscle and adipose tissue and provide a new avenue of investigation for obesity treatment or animal production. This review focuses on the roles of and crosstalk between myokines and adipokines in skeletal muscle and adipose tissue that modulate the molecular events in the metabolic homeostasis of the whole body.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Cell Communication; Humans; Interleukin-15; Interleukin-6; Interleukin-8; Mice; Muscle Cells; Muscle Proteins; Muscle, Skeletal; Obesity; Proteome; Signal Transduction

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; 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Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

It is well-known for a long-time, that intensive exercise is favourable for many metabolic parameters. Up-till now the exact mechanism has not been clarified. Recently it has turned out, that the muscular system is an extended endocrine organ, which, during contraction, secretes many hundred peptides, so called adipomyokines into the blood stream. Many of them improve glucose-utilization of the muscular system, and insulin-sensitivity, via endocrine, paracrine, or autocrine pathways. Worldwide intensive research takes place to clear up the exact pathomechanism of these processes. It came to light: 1. The newly discovered adipomyokine, irisin induces "browning" of beige precursor fat-cells, which are present in white adipose tissue. The developed beige adipose tissue by this way disposes with the advantegous properties of the brown adipose tissue. Taking together these facts, irisin might be a therapeutic choice in treating certain diseases, caused by inactive life-style. 2. Therapeutic application of brown adipose tissue in obesity, metabolic syndrome, and type 2 diabetes seems to be successful. This mechanism is based on removal of unnecessary calories via thermogenesis. 3. The role of myostatin, which is also produced by muscle contraction, is contradictory. It is not clear, why does the muscle system produce damaging product for the metabolism. On the other hand, inhibition of myostatin might be a therapeutic option. It is still questionable, whether the other hundreds of myokines could possess practicable roles on glucose, lipid, insulin secretion/effects. At present one can establish, that regular exercise is essential for the everyday practise, in order to optimise quality of life.. Régóta ismeretes, hogy az intenzív izommunka számos metabolikus paramétert kedvezően befolyásol. E folyamat mechanizmusa eddig nem volt tisztázott. Újabban kiderült, hogy a vázizomzat kiterjedt endokrin szerv, amely kontrakciója során több száz adipomiokint szekretál a véráramba, amelyek egy része endokrin, parakrin vagy autokrin úton javítja a vázizomzat glükózfelhasználását, fokozza inzulinérzékenységét. Világszerte intenzív kutatás igyekszik e folyamatok pontos mechanizmusát felderíteni. Három fontos területen történt előrehaladás: 1. Az újonnan felfedezett adipomiokin, az irisin a fehér zsírszövetben jelen lévő bézs prekurzor zsírsejtekben „barnásítást” indít meg, és az így létrejött bézs zsírszövet a továbbiakban a barna zsírszövet előnyös anyagcserehatásaival rendelkezik. Az irisin perspektivikusan terápiás opció lehet az inaktív életmód okozta betegségek kezelésében. 2. Kiderült, hogy a barna zsírszövet terápiás alkalmazása obesitasban, metabolikus szindrómában és 2-es típusú diabetesben eredményes, ami a felesleges kalóriák hőtermelés útján való eliminálásán alapszik. 3. Az ugyancsak kontrakció hatására termelődő myostatin szerepe ellentmondásos, nem világos, hogy az izomzat miért expresszál magára az izomzatra és az anyagcserére is káros anyagot, ugyanakkor a myostatin gátlása terápiásan felhasználható lehet. Kérdéses, hogy a többi sok száz miokinnek milyen szerepe lehet a fontos metabolikus paraméterek (glükóz, inzulin, lipidek) szekréciójában és hatásában, azonban a mindennapi gyakorlat számára már most leszögezhető, hogy a mozgás elengedhetetlen az életminőség optimalizálása szempontjából. Orv. Hetil., 2014, 155(37), 1469–1477.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Mass Index; Diabetes Mellitus, Type 2; Dietary Fats; Energy Metabolism; Fibronectins; Follistatin; Glucose; Humans; Inflammation; Insulin Resistance; Interleukin-15; Interleukin-6; Interleukin-8; Metabolic Syndrome; Muscle Contraction; Muscle, Skeletal; Myocardium; Myostatin; Obesity; Physical Exertion; Sedentary Behavior

Our meta-analysis was performed to estimate the effect of continuous positive airway pressure (CPAP) therapy on systemic inflammation in patients with obstructive sleep apnea (OSA).. A comprehensive literature search of PubMed and EMBASE was performed for literature published up to January 2013. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy.. A total of 35 studies involving 1985 OSA patients were included in the meta-analysis. Each study investigated one or more inflammatory markers: 24 studies on C-reactive protein (CRP), 16 studies on IL-6, 3 studies on IL-8, and 12 studies on tumor necrosis factor α (TNF-α). The results showed that the SMD (95% confidence interval [CI]) for CRP, IL-6, IL-8, and TNF-α were 0.452 (95% CI, 0.252-0.651), 0.299 (95% CI, 0.001-0.596), 0.645 (95% CI, 0.362-0.929), and 0.478 (95% CI, 0.219-0.736) in pre- and post-CPAP therapy, respectively. The subgroup analyses seemed to support better benefits with therapy duration of ≥3 months and more adequate compliance (≥4 h/night).. CPAP therapy could partially suppress systemic inflammation in OSA patients, and substantial differences were present among the various inflammatory markers.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Continuous Positive Airway Pressure; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive; Treatment Outcome; Tumor Necrosis Factor-alpha

White adipose tissue and skeletal muscle are the largest organs in the body and both are composed of distinct cell types. The signature cell of adipose tissue is the adipocyte while myocytes are the defining cell of skeletal muscle. White adipocytes are major secretory cells and this is increasingly apparent also for myocytes. Both cells secrete a range of bioactive proteins, generally termed adipokines in the case of adipocytes and myokines for muscle cells. There has, however, been some confusion over nomenclature and we suggest that the name myokine is restricted to a protein that is secreted from myocytes, while the term adipokine should be used to describe all proteins secreted from any type of adipocyte (white, brown or brite). These definitions specifically exclude proteins secreted from other cells within adipose tissue and muscle, including macrophages. There is some commonality between the myokines and adipokines in that both groups include inflammation-related proteins - for example, IL-6, Il-8 and MCP-1. Adipokines and myokines appear to be involved in local autocrine/paracrine interactions within adipose tissue and muscle, respectively. They are also involved in an endocrine cross-talk with other tissues, including between adipose tissue and skeletal muscle, and this may be bi-directional. For example, IL-6, secreted from myocytes may stimulate lipolysis in adipose tissue, while adipocyte-derived IL-6 may induce insulin resistance in muscle.

Topics: Adipocytes; Adipokines; Adipose Tissue; Adiposity; Animals; Cell Communication; Chemokine CCL2; Humans; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Mice; Muscle Cells; Muscle, Skeletal; Obesity; Rats

Osteoarthritis (OA), the most common form of arthritis, is associated with joint malfunction and chronic disability in the aged population. It is a multifactorial disorder to which several factors-such as age, sex, trauma, and obesity-contribute significantly. Obesity is one of the most influential but modifiable risk factors because it exerts an increased mechanical stress on the tibiofemoral cartilage. However, the high prevalence of OA in obese individuals in non-weightbearing areas, like finger joints, suggests that the link between being overweight and OA lies with factors other than simple biomechanics. An important correlation has been made between obesity and inflammation. Adipose tissues (and the infrapatellar fat pad) play an important role in this context because they are the major source of cytokines, chemokines, and metabolically active mediators called adipokines (or adipocytokines). These metabolic factors are known to possess catabolic and proinflammatory properties and to orchestrate the pathophysiological processes in OA. This review provides information on the relationship between obesity and OA through biomechanical and biochemical factors and highlights the functions of important obesity-related inflammatory products in the initiation and progression of OA. This information will broaden our thinking in identifying the targets for both prevention and intervention for OA.

Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Disease Models, Animal; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Leptin; Obesity; Osteoarthritis; Prevalence; Resistin; Risk Factors; Tumor Necrosis Factor-alpha

Activation of immunological and systemic inflammation markers are common in obesity and asthma.. The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients.. Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B).. The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences.. Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.

Topics: Adult; Asthma; Biomarkers; Body Mass Index; Cytokines; Diet, Reducing; Exercise; Female; Flow Cytometry; Humans; Immune System; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Systemic Inflammatory Response Syndrome; Treatment Outcome; Weight Loss; Weight Reduction Programs

Obesity is characterized by chronic low-grade inflammation driven by activation and tissue infiltration of circulating leukocytes. Although exercise has anti-inflammatory effects, the impact of exercise on mediators of leukocyte migration is unclear.. To determine the impact of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT), in the absence of weight/fat loss, on circulating chemokines and leukocyte chemokine receptors.. Thirty-seven inactive obese adults were randomized to 2 wk (10 sessions) of HIIT or MICT with fasting blood samples collected before and after training. Plasma concentration of C-C motif chemokine ligand 2 (CCL2; also known as monocyte chemoattractant protein-1), CCL3 (also known as macrophage inflammatory protein-1alpha), and C-X-C motif ligand 8 (CXCL8; also known as interleukin-8) were determined and the chemokine receptors CCR2, CCR5, and CXCR2 were measured on monocytes, neutrophils, and T cells.. MICT reduced the percentage of monocytes positive for CCR2 and reduced surface protein expression of CXCR2 on monocytes (both P < 0.05), whereas HIIT increased CCR5 surface protein expression and percentage CCR5 positive monocytes and neutrophils (all P < 0.05) along with increasing the percentage of T cells that were positive for CCR5 (P < 0.05). There were no significant changes in circulating chemokines, percent body fat or visceral adipose tissue.. Exercise, in the absence of weight/fat loss and without changes in circulating chemokines, has direct effects on leukocytes in obese adults with HIIT and MICT resulting in different responses. MICT may reduce monocyte migration potential through downregulation of CCR2 and CXCR2, whereas HIIT may increase potential for CCR5-mediated monocyte, neutrophil, and T-cell infiltration. The impact of different exercise protocols on leukocyte trafficking to tissues in obesity warrants further research.

Topics: Adult; Aged; Anthropometry; Chemokine CCL2; Chemokine CCL3; High-Intensity Interval Training; Humans; Interleukin-8; Leukocyte Count; Middle Aged; Obesity; Receptors, CCR2; Receptors, CCR5; Receptors, Interleukin-8B

Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk.. To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women.. Randomized, open-labelled parallel study.. Endocrinology outpatient clinic in a referral centre.. Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m. Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment.. After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment.. This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.

Topics: Biomarkers; Cannabinoid Receptor Antagonists; Cytokines; Female; Humans; Hyperandrogenism; Inflammation; Interleukin-8; Metformin; Obesity; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Vascular Endothelial Growth Factor A; Weight Loss

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; 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Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; 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To compare the effects of two interval exercises with different intensities on acute inflammatory response in lean and overweight-obese subjects.. Ten lean (BMI<24.9kg/m(2)) and 12 overweight-obese (BMI 25 to <34.9kg/m(2)) males performed two conditions in randomly assigned: (1) high intensity interval exercise (HIIE) 10×60s (85-90%PMax)/75s (50%PMax); (2) moderate intensity interval exercise (MIIE) 10×60s (70-75%PMax)/60s (50%PMax), with blood collections at pre, immediately and 30min post each exercise bouts to evaluate total and differential leukocyte counts, serum creatine kinase (CK), lactate dehydrogenase (LDH) and systemic levels of IL-1ra, IL-6, IL-8, IL-10, IL-17a and CCL2.. In lean group, HIIE induced a significant increase in total leukocytes and monocyte, while MIIE session did not change the number of leukocytes. Overweight-obese group presented similar increase in leukocytes, monocytes and lymphocytes in both HIIE and MIIE sessions. At baseline, overweight-obese group showed high levels of CK, IL-8, IL-6 and CCL2 and lower concentrations of IL-10 compared to lean group. The MIIE did not alter the cytokine concentrations in both groups, independently of the time analysis. The HIIE induced significant decrease in IL-8 levels 30min post session in both the groups, and a progressive elevation in IL-10 levels immediately and 30min post in lean and overweight-obese. Regarding IL-6, overweight-obese subjects presented progressive increase either immediately and 30min after HIIE, while lean individuals presented significant increase only 30min after exercise.. The acute inflammatory response to interval exercise is intensity-dependent. Although obesity influences the basal concentrations of several cytokines, only HIIE induced important alterations in IL-8 and IL-10 levels, which may have important implications in the control of chronic low-grade inflammation in obesity.

Topics: Adolescent; Adult; Body Mass Index; Chemokine CCL2; Creatine Kinase; Enzyme-Linked Immunosorbent Assay; Exercise; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; L-Lactate Dehydrogenase; Leukocyte Count; Male; Obesity; Overweight; Time Factors; Young Adult

Increasing physical activity in pregnancy may improve pregnancy outcomes for obese women. Exercise could reduce gestational weight gain, improve the maternal circulating lipid profile as well as alter leptin, Interleukin-8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1) levels.. The aim of this study was to investigate the effects of exercise on gestational weight gain, maternal circulating lipids, IL-8, MCP-1 and leptin levels in obese pregnant women.. The analysis was performed in the 35 obese women enrolled in the pilot BAMBINO randomised controlled trial who provided blood samples at 12- and 28-weeks gestation. Women in the exercise intervention arm received an individualised exercise plan. Blood samples, exercise diary and pedometer data were obtained at 12-, 20-, 28- and 36-weeks' gestation. Cord blood was obtained at delivery.. Women in the exercise arm exercised more than those in the control arm (P = 0.038). There was no difference in gestational weight gain, excess gestational weight gain, MCP-1 and leptin levels between women in the exercise intervention (n = 19) or the control arm (n = 16). IL-8 was not detectable. Exercise did not alter the maternal lipid profile.. The low level of physical activity achieved in obese women in the exercise intervention arm was insufficient to alter gestational weight gain, MCP-1, leptin or circulating lipid levels.

Topics: Adult; Chemokine CCL2; Exercise; Female; Humans; Interleukin-8; Leptin; Obesity; Pilot Projects; Pregnancy; Pregnancy Complications; Weight Gain; Young Adult

Long-chain omega 3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) exert potent anti-inflammatory properties in humans. This study characterized the effects of omega-3 ω-3 fatty acids supplements (ω-3 FA) on the inflammatory status in the placenta and adipose tissue of overweight/obese pregnant women.. A randomized, double-masked controlled trial was conducted in overweight/obese pregnant women that were randomly assigned to receive DHA plus EPA (2 g/day) or the equivalent of a placebo twice a day from week 10-16 to term. Inflammatory pathways were characterized in: 1) adipose tissue and placenta of treated vs. untreated women; and 2) adipose and trophoblast cells cultured with long chain FAs.. The sum of plasma DHA and EPA increased by 5.8 fold and ω-3 FA/ω-6 FA ratio was 1.5 in treated vs. untreated women (p< 0.005). Plasma CRP concentrations were reduced (p<0.001). The adipose tissue and placenta of treated women exhibited a significant decrease in TLR4 adipose and placental expression as well as IL6, IL8, and TNFα In vitro, EPA and DHA suppressed the activation of TLR4, IL6, IL8 induced by palmitate in culture of adipose and trophoblast cells.. Supplementation of overweight/obese pregnant women with dietary ω-3 FAs for >25 weeks reduced inflammation in maternal adipose and the placental tissue. TLR4 appears as a central target of the anti-inflammatory effects at the cellular level.. ClinicalTrials.gov NCT00957476.

Topics: Adipose Tissue; Adult; Diet; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Interleukin-8; Obesity; Placenta; Pregnancy; Primary Cell Culture; Signal Transduction; Toll-Like Receptor 4; Trophoblasts

Fibre intake among North Americans is currently less than half the recommended amount. Consumers are interested in food products that could promote weight loss and improve health. Consequently, evaluation of unique fibre sources with potential gut-mediated benefits for metabolic health warrants investigation. Our objective is to assess the effects of yellow pea fibre supplementation on weight loss and gut microbiota in an overweight and obese adult population.. In a double blind, placebo controlled, parallel group study, overweight and obese (BMI = 25-38) adults will be randomized to either a 15 g/d yellow pea fibre supplemented group or isocaloric placebo group for 12 weeks (n = 30/group). The primary outcome measure is a change in body fat from baseline to 12 weeks. Secondary outcomes include glucose tolerance, appetite regulation, serum lipids and inflammatory markers. Anthropometric data (height, weight, BMI, and waist circumference) and food intake (by 3-day weighed food records) will be measured at baseline and every 4 weeks thereafter. Subjective ratings of appetite will be recorded by participants at home on a weekly basis using validated visual analogue scales. At week 0 and at the end of the study (week 12), an ad libitum lunch buffet protocol for objective food intake measures and dual-energy X-ray absorptiometry (DXA) scan for body composition will be completed. Participants will be instructed not to change their exercise habits during the 12 week study. Glucose and insulin will be measured during an oral glucose tolerance test at weeks 0 and 12. Levels of lipids and CRP will be measured and inflammatory markers (adiponectin, leptin, TNF-α, IL-6 and IL-8) in the serum will be quantified using Milliplex kits. Mechanisms related to changes in gut microbiota, serum and fecal water metabolomics will be assessed.. Globally the development of functional foods and functional food ingredients are critically needed to curb the rise in metabolic disease. This project will assess the potential of yellow pea fibre to improve weight control via gut-mediated changes in metabolic health in overweight and obese adults.. ClinicalTrials.gov (NCT01719900) Registered October 23, 2012.

Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Adult; Aged; Appetite; Body Composition; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Interleukin-6; Interleukin-8; Intestines; Leptin; Male; Microbiota; Middle Aged; Obesity; Overweight; Pisum sativum; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss; Young Adult

Obesity is associated with low-grade chronic inflammation, which contributes to cellular dysfunction promoting metabolic disease. Obesity during pregnancy leads to a proinflammatory milieu in the placenta; however, the underlying causes for obesity-induced placental inflammation remain unclear. Here, we examine the mechanisms by which saturated fatty acids and inflammatory cytokines induce inflammation in placental trophoblasts. We conducted global transcriptomic profiling in BeWo cells following palmitate and/or TNFα treatment and gene/protein expression analyses of MAPK pathways and characterized downstream transcription factors directly regulating inflammatory cytokines. Microarray analysis revealed increased expression of genes regulating inflammation, stress response, and immediate early response in cytotrophoblasts in response to palmitic acid (PA), TNFα, or a combination of both (PA + TNFα). Both gene ontology and gene set enrichment analysis revealed MAPK and EGR-1 signaling to be upregulated in BeWo cells, which was confirmed via immunoblotting. Importantly, activation of JNK signaling was necessary for increased proinflammatory cytokine (IL-6, TNFα, and IL-8) and EGR1 mRNA. Consistent with the requirement of JNK signaling, ChIP analysis confirmed the recruitment of c-Jun and other MAPK-responsive immediate early factors on the EGR1 promoter. Moreover, recruitment of EGR-1 on cytokine promoters (IL-6, TNFα, and IL-8) and an impaired proinflammatory response following knockdown of EGR-1 suggested it as a central component of the mechanism facilitating inflammatory gene expression. Finally, akin to in vitro findings, term placenta from obese women also had both increased JNK and p38 signaling and greater EGR-1 protein relative to lean women. Our results demonstrate that lipotoxic insults induce inflammation in placental cells via activation of JNK/EGR-1 signaling.

Topics: Activating Transcription Factor 3; Cell Line; Early Growth Response Protein 1; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Lipid Metabolism; Male; MAP Kinase Signaling System; Obesity; Palmitates; Placenta; Pregnancy; Pregnancy Complications; Serum Response Factor; Transcriptome; Trophoblasts; Tumor Necrosis Factor-alpha

To determine the independent effect of long-term physical activity (PA) and the combined effects of long-term PA and weight loss (WL) on inflammation in overweight and obese older adults.. Eighteen-month randomized, controlled trial.. The community infrastructure of cooperative extension centers.. Overweight and obese (body mass index >28.0 kg/m(2) ) community-dwelling men and women aged 60 to 79 at risk for cardiovascular disease (CVD).. Physical activity + weight loss (PA + WL) (n = 98), PA only (n = 97), or successful aging (SA) health education (n = 93) intervention.. Biomarkers of inflammation (adiponectin, leptin, high-sensitivity interleukin (hsIL)-6, IL-6sR, IL-8, and soluble tumor necrosis factor receptor 1) were measured at baseline and 6 and 18 months.. After adjustment for baseline biomarker, wave, sex, and visit, leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin was significantly lower in the PA + WL group (21.3 ng/mL, 95% confidence interval (CI) = 19.7-22.9 ng/mL) than in the PA (29.3 ng/mL, 95% CI = 26.9-31.8 ng/mL) or SA (30.3 ng/mL, 95% CI = 27.9-32.8 ng/mL) group (both P < .001), and hsIL-6 was significantly lower in the PA + WL group (2.1 pg/mL, 95% CI = 1.9-2.3 pg/mL) than in the PA (2.5 pg/mL, 95% CI = 2.3-2.7 pg/mL) or SA (2.4 pg/mL, 95% CI = 2.2-2.6 pg/mL) group (P = .02).. Addition of dietary-induced WL to PA reduced leptin and hsIL-6 more than PA alone and more than a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile.

Topics: Adiponectin; Aged; Analysis of Variance; Biomarkers; Community Health Centers; Diet, Reducing; Exercise; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; North Carolina; Obesity; Overweight; Receptors, Tumor Necrosis Factor, Type I; Treatment Outcome; Weight Loss

Inflammation is a key feature of obesity and type 2 diabetes. The active vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH)₂D], modulates the inflammation in vitro. We studied whether inflammation in adipose tissue (AT) cultures could be reduced by incubation with 1,25(OH)₂D in vitro, or by oral treatment with vitamin D in vivo in obese subjects with low plasma levels of 25-hydroxyvitamin D. Samples of subcutaneous AT were stimulated with IL-1β to induce inflammation. In the in vitro study, samples were concomitantly incubated with or without 1,25(OH)₂D, and analyzed for mRNA and protein levels of inflammatory markers IL-6, IL-8, and MCP-1. In the in vivo study, samples of subcutaneous AT from obese subjects obtained before and after treatment with 7,000 IU of vitamin D daily or placebo in a randomized controlled trial were stimulated with IL-1β. The samples were analyzed for AT gene expression and compared with plasma markers of inflammation. In the in vitro study, concomitant incubation with 1,25(OH)₂D reduced mRNA levels of MCP-1 by 45% (p=0.01), of IL-6 by 32% (p=0.002), and of IL-8 by 34% (p=0.03), and reduced secretion of IL-8 protein by 18% (p=0.005). In vivo treatment with vitamin D did not reduce AT expression or circulating levels of MCP-1, IL-6, or IL-8. 1,25(OH)₂D has significant anti-inflammatory effects in AT in vitro. However, a similar reduction in AT and systemic inflammation cannot be obtained by oral treatment with vitamin D in obese subjects.

Topics: Adipose Tissue; Adult; Anti-Inflammatory Agents; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Vitamin D

We performed this study to examine the metabolic differences arising from higher liver fat accumulation in obese Hispanic adolescents, with a particular focus on circulating levels of adipocytokines and insulin resistance.. Forty-one obese Hispanic adolescents (15.3 ± 1.0 years, body mass index percentile: 97.0 ± 3.9) were assessed for: visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat fraction (HFF) by magnetic resonance imaging; fasting measures of serum glucose, insulin and adipocytokines; homeostasis model assessment of insulin resistance (HOMA-IR); and insulin sensitivity (SI) and the acute insulin response to glucose (AIR) by intravenous glucose tolerance test. Subjects with normal levels of HFF (below 5%; n = 25) were compared to those with HFF > 5% (n = 16).. The two groups differing in HFF were similar for total body fat, VAT and SAT. The group with HFF > 5% had significantly (P < 0.05) higher interleukin-8 (IL-8) (6.1 ± 1.6 vs. 3.2 ± 0.4 pg mL(-1) ), NGF (30.2 ± 9.9 vs. 13.9 ± 1.6 pg mL(-1) ), HOMA-IR (8.8 ± 1.1 vs. 5.5 ± 0.5), AIR (1869 ± 206 vs. 1092 ± 165) and a tendency for lower SI (1.2 ± 0.4 vs. 2.1 ± 0.3; P = 0.06), with no significant differences in any of other factors measured.. These data suggest that elevated liver fat is most closely associated with elevated serum IL-8 and NGF levels as well as increased AIR and HOMA-IR. These elevated factors may play significant roles in the metabolic abnormalities associated with elevated liver fat in obese Hispanics.

Topics: Adipokines; Adolescent; Blood Glucose; Body Composition; California; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Liver; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-8; Male; Nerve Growth Factor; Non-alcoholic Fatty Liver Disease; Obesity; Patient Education as Topic

An imbalance between pro- and anti-inflammatory cytokine productions in adipose tissue is thought to contribute to chronic, systemic, low-grade inflammation and consequently to an increased risk of cardiovascular complications in obese and type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels are elevated in such patients, have been shown to interfere with cytokine production in vitro. In order to evaluate the effects of elevated NEFA levels on cytokine production in adipose tissue in vivo we used an 18-gauge open-flow microperfusion (OFM) catheter to induce local inflammation in the subcutaneous adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF) specifically from the inflamed tissue. In two crossover studies, nine subjects received either an intravenous lipid-heparin infusion to elevate circulating NEFA levels or saline over a period of 28 h. The former increased the circulating levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period. NEFA effects on locally induced inflammation were estimated by measuring the levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) levels increased during the study period but were not affected by lipid-heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine, was significantly reduced during the final hour of lipid-heparin infusion (saline: 449.2 ± 105.9 vs. lipid-heparin: 65.4 ± 15.4 pg/ml; P = 0.02). These data provide the first in vivo evidence that elevated NEFA can modulate cytokine production by adipose tissue.

Topics: Adipokines; Adult; Blood Glucose; Catheters; Chemokine CCL2; Cross-Over Studies; Cytokines; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Heparin; Humans; Inflammation; Insulin; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Male; Obesity; Retrospective Studies; Subcutaneous Fat; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult

Weight gain in young women suggests that childbearing may be an important contributor to the development of obesity in women. Depressive symptoms can interfere with resumption of normal activity levels following childbirth or with the initiation of or adherence to physical activity programs essential for losing pregnancy weight. Depression symptoms may function directly to promote weight gain through a physiologic mechanism. Obesity and its related insulin resistance may contribute to depressed mood physiologically. Although physical activity has well-established beneficial effects on weight management and depression, women tend to under participate in physical activity during childbearing years. Further, the mechanisms underpinning the interplay of overweight, obesity, physical activity, depression, and inflammatory processes are not clearly explained.. This report describes the theoretical rationale, design considerations, and cultural relevance for "Madres para la Salud" [Mothers for Health].. Madres para la Salud is a 12 month prospective, randomized controlled trial exploring the effectiveness of a culturally specific intervention using "bouts" of physical activity to effect changes in body fat, systemic and fat tissue inflammation, and postpartum depression symptoms in sedentary postpartum Latinas.. The significance and innovation of Madres para la Salud includes use of a theory-driven approach to intervention, specification and cultural relevance of a social support intervention, use of a Promotora model to incorporate cultural approaches, use of objective measures of physical activity in post partum Latinas women, and the examination of biomarkers indicative of cardiovascular risk related to physical activity behaviors in postpartum Latinas.

Topics: Body Composition; C-Reactive Protein; Cardiovascular Diseases; Community Health Workers; Depression; Environment Design; Exercise; Female; Health Promotion; Hispanic or Latino; Humans; Inflammation; Interleukin-6; Interleukin-8; Obesity; Plasminogen Activator Inhibitor 1; Postpartum Period; Safety; Social Support; Walking

In view of the previously described anti-inflammatory effects of insulin, we investigated the potential suppressive effect of insulin on plasma concentrations and expression of the chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES) and their receptors, chemokine receptor (CCR)-2 and CCR-5, in mononuclear cells (MNCs). We also investigated the effect of insulin on other chemokines.. Ten obese type 2 diabetic patients were infused with insulin (2 units/h with 100 ml of 5% dextrose/h) for 4 h. Another 8 and 6 type 2 diabetic patients were infused with 100 ml of 5% dextrose/h or saline for 4 h, respectively, and served as control subjects. Blood samples were obtained at 0, 2, 4, and 6 h.. Insulin infusion significantly suppressed the plasma concentrations of MCP-1, eotaxin, and RANTES and the expression of RANTES, macrophage inflammatory protein (MIP)-1beta, CCR-2, and CCR-5 in MNCs at 2 and 4 h. Dextrose and saline infusions did not alter these indexes.. A low-dose infusion of insulin suppresses the plasma concentration of key chemokines, MCP-1, and RANTES, and the expression of their respective receptors, CCR-2 and CCR-5, in MNCs. Insulin also suppresses the expression of RANTES and MIP-1beta in MNCs. These actions probably contribute to the comprehensive anti-inflammatory effect of insulin.

Topics: Adult; Blood Glucose; Chemokine CCL11; Chemokine CCL4; Chemokine CCL5; Chemokine CX3CL1; Chemokine CXCL12; Chemokines; CX3C Chemokine Receptor 1; Diabetes Mellitus, Type 2; Gene Expression; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Inflammation; Infusions, Intravenous; Insulin; Interleukin-8; Middle Aged; Obesity; Receptors, CCR2; Receptors, CCR5; Receptors, Chemokine; Receptors, CXCR4

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin (P < 0.001) increased, and C-reactive protein (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.05), and monocyte chemoattractant protein-1 (P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin (P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-alpha (P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased (P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.

Topics: Adiponectin; Adipose Tissue; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Blood Pressure; Body Weight; C-Reactive Protein; Chemokine CCL2; Diet; Exercise; Female; Gene Expression; Glucose Tolerance Test; Humans; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Macrophages; Male; Muscle, Skeletal; Obesity; Receptors, Adiponectin; Receptors, Cell Surface; Tumor Necrosis Factor-alpha

Little is known about common factors (e.g., macronutrients and energy supply) regulating the protein secretory function of adipose tissue. We therefore compared the effects of randomly assigned 10-week hypoenergetic (-600 kcal/day) diets with moderate-fat/moderate-carbohydrate or low-fat/high-carbohydrate content on circulating levels and production of proteins (using radioimmunoassays and enzyme-linked immunosorbent assays) from subcutaneous adipose tissue in 40 obese but otherwise healthy women. Similar results were obtained by the two diets. Body weight decreased by approximately 7.5%. The secretion rate of leptin decreased by approximately 40%, as did that of tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 and -8 decreased by 25-30%, whereas the secretion of plasminogen activator inhibitor 1 (PAI-1) and adiponectin did not show any changes. Regarding mRNA expression (by real-time PCR), only that of leptin and IL-6 decreased significantly. Circulating levels of leptin and PAI-1 decreased by 30 and 40%, respectively, but there were only minor changes in circulating TNF-alpha, IL-6, or adiponectin. In conclusion, moderate caloric restriction but not macronutrient composition influences the production and secretion of adipose tissue-derived proteins during weight reduction, leptin being the most sensitive and adiponectin and PAI-1 the least sensitive.

Topics: Adipose Tissue; Adult; Body Mass Index; Diet, Reducing; Female; Humans; Interleukin-6; Interleukin-8; Leptin; Obesity; Patient Compliance; Plasminogen Activator Inhibitor 1; Proteins; RNA, Messenger; Tumor Necrosis Factor-alpha

Low-grade chronic inflammation is one of the main disorders that characterize adipose tissue dysfunction in obesity and is an important element in the pathogenesis of several comorbidities. In this context, selenium is an essential micronutrient that exerts important anti-inflammatory functions, and the role of selenium in controlling inflammation associated with obesity is not well defined. Thus, this study aimed to evaluate the relationship between markers of the nutritional status of selenium and low-grade chronic inflammation in obese women. This cross-sectional study included 81 women aged between 18 and 50 years, who were divided into two groups according to body mass index (BMI): the obesity group (n = 38) and normal weight group (n = 43). Selenium intake was assessed by 3-day diet records. The plasma, erythrocyte, and urinary selenium concentrations were determined using inductively coupled plasma optical emission spectrometry. The analysis of serum cytokines interleukin (IL)-8, IL-1β, IL-6, IL-10, and tumor necrosis factor alpha (TNFα) was performed using flow cytometry. The results of this study revealed that the obese women had higher dietary intake of selenium than eutrophic women. However, obese participants showed decreased selenium concentrations in plasma and erythrocytes, in parallel with increased concentrations of selenium in the urine. Regarding the inflammatory parameters, obese women exhibited higher concentrations of IL-6 and lower concentrations of the cytokines IL-8, IL-1β, and TNFα than eutrophic women. In the binary logistic regression analysis, erythrocyte selenium was considered an independent predictor of the serum concentrations of cytokine IL-8 in obese women, reflecting the anti-inflammatory action of this micronutrient.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Body Mass Index; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Micronutrients; Middle Aged; Nutritional Status; Obesity; Selenium; Tumor Necrosis Factor-alpha; Young Adult

A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB).. This cross-sectional study included 1194 men and women with a median age of 24.5 ± 3.12 years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups.. Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p ≤ 0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p < 0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r ≥ 0.24; p < 0.001), and negatively with interleukin-10 (all r ≤ -0.13; p < 0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p < 0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all ≥ 263 %), leptin (all ≥ 175 %), interleukin-6 (all ≥ 134 %), and tumour necrosis factor-α (all ≥ 26 %), and lower for adiponectin (all ≥ 57 %), interleukin-10 (all ≥ 9 %), and interleukin-8 (all ≥ 15 %) compared to being in the bottom quartile.. The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof.

Topics: Adiponectin; Adiposity; Adult; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Heart Disease Risk Factors; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Overweight; Prospective Studies; Pulse Wave Analysis; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult

The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study.. Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH.. After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (. Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth.

Topics: Adiposity; Birth Weight; Cytokines; Female; Growth Hormone; Humans; Interleukin-8; Obesity; Placenta; Pregnancy; Pregnancy Outcome; Pregnant Women; Race Factors

Adiponectin (ADIPO) and interleukin-8 (IL-8) are proteins that play a significant, albeit opposing, role in metabolic syndrome (MetS). The reported data on the effect of physical activity on the levels of these hormones in the population of people with MetS are conflicting. The aim of the study was to evaluate the changes in hormone concentrations, insulin-resistance indices and body composition after two types of training. The study included 62 men with MetS (age 36.6 ± 6.9 years, body fat [BF] = 37.53 ± 4.5%), randomly assigned to: an experimental group EG1 (n = 21) with aerobic exercise intervention, an experimental group EG2 (n = 21) with combined aerobic and resistance exercise intervention, both for 12 weeks, and a control group CG (n = 20) without interventions. Anthropometric measurements and body composition (fat-free mass [FFM], gynoid body fat [GYNOID]), as well as a biochemical blood analysis (adiponectin [ADIPO], interleukin-8 [IL-8], homeostatic model assessment-adiponectin (HOMA-AD) and homeostatic model assessment-triglycerides (HOMA-TG) were performed at baseline, and at 6 and 12 weeks of intervention and 4 weeks after the intervention (follow-up). Intergroup (between groups) and intragroup (within each group) changes were statistically evaluated. In the experimental groups EG1 and EG2, no significant changes were observed in the ADIPO concentration, but a decrease of GYNOID and insulin-resistance indices was confirmed. The aerobic training led to favorable changes in IL-8 concentration. The use of combined resistance and aerobic training led to improved body composition, decreased waist circumference and better insulin-resistance indices in men with MetS.

Topics: Adiponectin; Adult; Arrhythmias, Cardiac; Body Mass Index; Carbohydrate Metabolism; Humans; Insulin; Insulin Resistance; Interleukin-8; Male; Metabolic Syndrome; Obesity

Obesity and preeclampsia both involve a pathological inflammatory response, which may be how obesity increases preeclampsia risk. Previous studies have failed to assess robust measurements of inflammatory markers across gestation, specifically in overweight/ obese women in the context of preeclampsia.. We measured 20 inflammatory markers in plasma via multiplex assay (ThermoFisher Inflammation 20 plex Human ProcartaPlex Panel) across the three trimesters of pregnancy in an existing cohort of overweight and obese women who developed preeclampsia (n = 37) and without preeclampsia (n = 74). Mann-Whitney U tests examined differences in inflammatory marker concentrations between cases and controls. Repeated measures ANOVA tests were used to explore differences in inflammatory marker concentrations over time within cases and controls.. Pro-inflammatory markers (IL-1α, IL-1β, IL-6, IFN-α, IFN-γ, GM-CSF, IL-12p70, IL-17α, TNF-α, IL-8) and anti-inflammatory markers (IL-4, IL-10, IL-13) were higher in the first and second trimester in participants who later developed preeclampsia compared to those who did not (p < .05). Only TNF-α and IL-8 remained elevated in the third trimester. Inflammatory markers did not change across pregnancy in preeclampsia cases but did increase across pregnancy in controls.. Our findings diverge from prior studies, predominantly of non-obese women, that report lower circulating concentrations of anti-inflammatory cytokines in preeclampsia versus normotensive pregnancy, particularly by late pregnancy. We posit that women with overweight and obesity who develop preeclampsia entered pregnancy with a heightened pro-inflammatory state likely related to obesity, which increased risk for preeclampsia. Further studies are needed to investigate if inflammatory maker profiles differ between obese and non-obese women.

Topics: Female; Humans; Interleukin-8; Obesity; Overweight; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha

The therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4

Topics: Adipose Tissue; CD4-Positive T-Lymphocytes; CD40 Ligand; Cells, Cultured; Chemokines; Humans; Interleukin-8; NF-kappa B; Obesity; Stromal Cells; T-Lymphocytes; Tumor Necrosis Factor-alpha

What is the central question of this study? Is 1 week of exercise training sufficient to reduce local and systemic inflammation? Do obesity and short-term concurrent aerobic and resistance exercise training alter skeletal muscle extracellular vesicle (EV) contents? What is the main finding and its importance? Obesity alters skeletal muscle small EV microRNAs targeting inflammatory and growth pathways. Exercise training alters skeletal muscle small EV microRNAs targeting inflammatory pathways, indicative of reduced inflammation. Our findings provide support for the hypotheses that EVs play a vital role in intercellular communication during health and disease and that EVs mediate many of the beneficial effects of exercise.

Topics: Exercise; Extracellular Vesicles; Humans; Inflammation; Interleukin-8; MicroRNAs; Muscle, Skeletal; Obesity; Phosphatidylinositol 3-Kinases; RNA, Messenger

Extracellular matrix (ECM) components released during excessive fat mass expansion are considered potential endogenous danger/alarm signals contributing to innate immune system activation. The aim of the current study was to specifically measure plasma levels of low molecular weight (LMW) hyaluronan (HA) and to evaluate its role as pro-inflammatory damage-associated molecular pattern (DAMP) on leukocyte response in the context of human obesity.. Participants were selected according to their body mass index (BMI, kg/m. We observed a statistically significant increase in the circulating levels of HA fragments of LMW in individuals with obesity which were consistent with significant up-regulated expression of the LMW HA synthesizing enzyme hyaluronan synthase-1 (HAS-1) in obese adipose tissue. Gene expression assessment of HA receptors revealed up-regulated levels for TLR2 in both obese PMN and PBMC. Synthetic HA molecules of different sizes were tested on leukocytes from healthy donors. LMW HA fragments (15-40 kDa) and not those from intermediate molecular sizes (75-350 kDa) induced a significant up-regulation of the expression of major pro-inflammatory cytokines such as IL-1β, MCP-1 and IL-8 in PBMC. Importantly, LMW HA was able to induce the phosphorylation of IKK α/β complex supporting its pro-inflammatory role through NF-κB activation.. Circulating LMW HA molecules are elevated in obesity and may play an important role in triggering low-grade inflammation and the development of metabolic complications.

Topics: Cytokines; Ficoll; Humans; Hyaluronan Synthases; Hyaluronic Acid; I-kappa B Kinase; Immunity, Innate; Inflammation; Interleukin-8; Leukocytes, Mononuclear; NF-kappa B; Obesity; Toll-Like Receptor 2

Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease.. This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test.. The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell.. This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.

Topics: Adipokines; Adipose Tissue; Breast Neoplasms; Cadherins; Cell Line, Tumor; Cytokines; Female; Humans; Inflammatory Breast Neoplasms; Interleukin-6; Interleukin-8; Obesity

Adipose tissue secretions are depot-specific and vary based on anatomical location. Considerable attention has been focused on visceral (VAT) and subcutaneous (SAT) adipose tissue with regard to metabolic disease, yet our knowledge of the secretome from these depots is incomplete. We conducted a comprehensive analysis of VAT and SAT secretomes in the context of metabolic function. Conditioned media generated using SAT and VAT explants from individuals with obesity were analyzed using proteomics, mass spectrometry, and multiplex assays. Conditioned media were administered in vitro to rat hepatocytes and myotubes to assess the functional impact of adipose tissue signaling on insulin responsiveness. VAT secreted more cytokines (IL-12p70, IL-13, TNF-α, IL-6, and IL-8), adipokines (matrix metalloproteinase-1, PAI-1), and prostanoids (TBX2, PGE2) compared with SAT. Secretome proteomics revealed differences in immune/inflammatory response and extracellular matrix components. In vitro, VAT-conditioned media decreased hepatocyte and myotube insulin sensitivity, hepatocyte glucose handling, and increased basal activation of inflammatory signaling in myotubes compared with SAT. Depot-specific differences in adipose tissue secretome composition alter paracrine and endocrine signaling. The unique secretome of VAT has distinct and negative impact on hepatocyte and muscle insulin action.

Topics: Adipokines; Animals; Culture Media, Conditioned; Dinoprostone; Glucose; Humans; Insulin Resistance; Interleukin-13; Interleukin-6; Interleukin-8; Intra-Abdominal Fat; Isophane Insulin, Human; Matrix Metalloproteinase 1; Obesity; Plasminogen Activator Inhibitor 1; Rats; Secretome; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett's Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma. To that end, we analyzed the expression of the rate-limiting enzyme, carnitine palmytoyltransferase 1A (CPT1A), in human tissues and cell lines representing different stages in the sequence from normal squamous esophagus to cancer. We determined uptake of palmitic acid, the most abundant fatty acid in human serum, with fluorescent dye-labeled lipids as well as functional consequences of stimulation with palmitic acid relevant to Barrett's tumorigenesis, e.g., proliferation, characteristics of stemness and IL8 mediated inflammatory signaling. We further employed different mouse models including a genetic model of Barrett's esophagus based on IL1β overexpression in the presence and absence of a high fat diet and deoxycholic acid to physiologically mimic gastrointestinal reflux in the mice. Together, our data demonstrate that CPT1A is upregulated in Barrett's tumorigenesis and that experimental palmitic acid is delivered to mitochondria and associated with increased cell proliferation and stem cell marker expression.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Carcinogenesis; Carnitine; Carnitine O-Palmitoyltransferase; Cell Proliferation; Cell Transformation, Neoplastic; Deoxycholic Acid; Esophageal Neoplasms; Fluorescent Dyes; Gastroesophageal Reflux; Humans; Interleukin-8; Mice; Obesity; Palmitic Acid

Obesity is resulted from energy surplus and is characterized by abnormal adipose tissue accumulation and/or distribution. Adipokines secreted by different regional adipose tissue can induce changes in key proteins of the insulin signaling pathway in hepatocytes and result in impaired hepatic glucose metabolism. This study aimed to investigate whether exenatide affects key proteins of IRS2/PI3K/Akt2 signaling pathway in hepatocytes altered by the different regional fat depots. Six non-obese patients without endocrine diseases were selected as the research subjects. Their subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)were co-cultured with HepG2 cells in the transwell chamber. In the presence or absence of exenatide, adipokines content in the supernatant of each experimental group was detected by ELISA. In addition, HepG2 cells in each co-culture group with and without insulin were collected, and the expression of key proteins IRS2, p-IRS2(S731), PI3K-p85, Akt2, and p-Akt2(S473) was detected by western blotting (WB). The results showed that the adipokines IL-8, MCP-1, VEGF, and sTNFR2 in the supernatant of HepG2 cells induced by different regional adipose tissue were significantly higher than those in the HepG2 group, and VAT released more adipokines than SAT. Furthermore, these adipokines were significantly inhibited by exenatide. Importantly, the different regional fat depot affects the IRS2/PI3K/Akt2 insulin signaling pathway of hepatocytes. Exenatide can up-regulate the expression of hepatocyte proteins IRS2, PI3K-p85, p-Akt2(S731) inhibited by adipose tissue, and down-regulate the expression of hepatocyte proteins p-IRS2(S731) promoted by adipose tissue. The effect of VAT on the expression of these key proteins in hepatocytes is more significant than that of SAT. But there was no statistical difference in the expression of Akt2 protein among each experimental group, suggesting that exenatide has no influence on the expression of Akt2 protein in hepatocytes. In conclusion, exenatide may improve hepatic insulin resistance (IR) by inhibiting adipokines and regulating the expression of key proteins in the IRS2/PI3K/Akt2 pathway.

Topics: Adipokines; Adipose Tissue; Exenatide; Glucose; Hepatocytes; Humans; Insulin; Insulin Resistance; Interleukin-8; Obesity; Phosphatidylinositol 3-Kinases; Vascular Endothelial Growth Factor A

We studied the effect of combined antimicrobial therapy with amoxicillin, metronidazole, and clarithromycin on the severity of ischemia/reperfusion myocardial injury in Wistar rats with alimentary obesity and acute inflammation of the large intestine. General ischemia/reperfusion was reproduced on Langendorff-perfused isolated hearts and infarct size was estimated. Acute inflammation of the large intestine was accompanied by an increase in the blood levels of proinflammatory cytokines. The presence of obesity and acute inflammation of the large intestine did not significantly affect the infarct size in comparison with the control. Administration of antimicrobial drugs to animals with obesity and acute inflammation of the large intestine led to a significant increase in the infarct size, which should be considered when prescribing antimicrobial therapy to patients with comorbidity.

Topics: Alkaline Phosphatase; Animals; Anti-Infective Agents; Bifidobacterium; Body Weight; Inflammation; Interleukin-8; Intestine, Large; Lactobacillus; Male; Myocardial Reperfusion Injury; Myocardium; Obesity; Random Allocation; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Topics: Caveolin 1; Cells, Cultured; Humans; Inflammation; Interleukin-6; Interleukin-8; Keratinocytes; Leptin; Obesity; Psoriasis

The incidence of obesity-related asthma has shown a remarkable increase.. We aimed to explore the role of heat shock protein 72 (Hsp72) and receptor for advanced glycation end products (RAGE) axis with its downstream signaling in the pathogenesis of obesity-related asthma.. We enrolled a total of 55 subjects and divided them into three groups. Groups I and II included healthy, normal weight (n = 15) and obese (n = 15) subjects, respectively. Twenty-five obese asthmatics (group III) were subdivided into group IIIa (10 patients with mild to moderate asthma) and group IIIb (15 patients with severe asthma). High mobility group box 1 (HMGB1), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and urinary Hsp72 were immunoassayed. Hydrogen peroxide (H. The current study highlights the role of Hsp72 and HMGB1/RAGE/ERK1/2 signaling cascade in the pathogenesis of bronchial asthma and its link to obesity, which could be reflected on monitoring, severity grading, and management of this disease.

Topics: Adult; Antigens, Neoplasm; Asthma; Case-Control Studies; Chemokine CCL2; Fatty Acids, Nonesterified; Female; Heat-Shock Proteins; HMGB1 Protein; Humans; Hydrogen Peroxide; Interleukin-8; Male; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinases; Molecular Chaperones; Obesity; Receptor Cross-Talk

Obese individuals seem to be at the highest risk of contracting COVID-19 infection. Furthermore, severity of morbidity and mortality rates are higher in the developed world as compared to the developing world. One probable reason for this difference could be the difference in living conditions and exposure to other infections. Secondly, the difference in food especially, alcohol use may have deteriorating effects superimposed with obesity. Our hypothesis suggests that a combination of alcohol consumption and obesity causes low immunity and makes the individual prone to develop 'cytokine storm' and 'acute respiratory distress syndrome'; the hallmark of COVID-19 mortality and morbidity. Thus, we propose that reducing any one trigger can have a beneficial effect in combating the disease severity.

Topics: Adipose Tissue; Alcohol Drinking; Alcoholism; Angiotensin-Converting Enzyme 2; China; COVID-19; Cytokines; Humans; Immune System; Inflammation; Interleukin-8; Obesity; Treatment Outcome; Tumor Necrosis Factor-alpha

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.

Topics: Adipocytes; Adipose Tissue; Animals; Arrhythmias, Cardiac; Cell Differentiation; Cell Movement; Chemokine CCL2; Diet, High-Fat; Genetic Diseases, X-Linked; Gigantism; Glucose Transporter Type 4; Heart Defects, Congenital; Inflammation; Insulin Resistance; Intellectual Disability; Interferons; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Lipopolysaccharides; Macrophages; Mice, Inbred C57BL; Mice, Obese; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Interleukin; Up-Regulation

Topics: Adiposity; Bariatric Surgery; Biomarkers; Caloric Restriction; Case-Control Studies; Diet, Ketogenic; Female; Fibronectins; Humans; Interleukin-8; Male; Matrix Metalloproteinase 2; Muscle, Skeletal; Obesity; Spain; Time Factors; Treatment Outcome; Weight Loss

Type 2 Diabetes (T2D) is strongly associated with obesity and inflammation. Toll-like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its ligands and downstream products increased systemically in T2D and in at-risk individuals. Detailed mechanisms of the complex proinflammatory response in pancreatic islets remain unknown. In isolated human islets LPS induced IL-1β, IL-6, IL-8 and TNF production in a TLR4-dependent manner and severely impaired β-cell survival and function. IL-6 antagonism improved β-cell function. IL-8, which was identified specifically in α-cells, initiated monocyte migration, a process fully blocked by IL-8 neutralization. The TLR4 response was potentiated in obese donors; with higher IL-1β, IL-6 and IL-8 expression than in non-obese donors. TLR4 activation leads to a complex multi-cellular inflammatory response in human islets, which involves β-cell failure, cytokine production and macrophage recruitment to islets. In obesity, the amplified TLR4 response may potentiate β-cell damage and accelerate diabetes progression.

Topics: Apoptosis; Cell Movement; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Disease Progression; Gene Expression Regulation; Humans; Inflammation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-1beta; Interleukin-6; Interleukin-8; Islets of Langerhans; Macrophages; Obesity; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Progression from BE to cancer is associated with obesity, possibly due to increased abdominal pressure and gastroesophageal reflux disease, although this pathogenic mechanism has not been proven. We investigated whether environmental or dietary factors associated with obesity contribute to the progression of BE to EAC in mice.. Tg(ED-L2-IL1RN/IL1B)#Tcw mice (a model of BE, called L2-IL1B mice) were fed a chow (control) or high-fat diet (HFD) or were crossbred with mice that express human interleukin (IL) 8 (L2-IL1B/IL8 mice). Esophageal tissues were collected and analyzed for gene expression profiles and by quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry. Organoids were established from BE tissue of mice and cultured with serum from lean or obese individuals or with neutrophils from L2-IL1B mice. Feces from mice were analyzed by 16s ribosomal RNA sequencing and compared to 16s sequencing data from patients with dysplasia or BE. L2-IL1B were mice raised in germ-free conditions.. L2-IL1B mice fed an HFD developed esophageal dysplasia and tumors more rapidly than mice fed the control diet; the speed of tumor development was independent of body weight. The acceleration of dysplasia by the HFD in the L2-IL1B mice was associated with a shift in the gut microbiota and an increased ratio of neutrophils to natural killer cells in esophageal tissues compared with mice fed a control diet. We observed similar differences in the microbiomes from patients with BE that progressed to EAC vs patients with BE that did not develop into cancer. Tissues from dysplasias of L2-IL1B mice fed the HFD contained increased levels of cytokines that are produced in response to CXCL1 (the functional mouse homolog of IL8, also called KC). Serum from obese patients caused organoids from L2-IL1B/IL8 mice to produce IL8. BE tissues from L2-IL1B mice fed the HFD and from L2-IL1B/IL8 mice contained increased numbers of myeloid cells and cells expressing Cxcr2 and Lgr5 messenger RNAs (epithelial progenitors) compared with mice fed control diets. BE tissues from L2-IL1B mice raised in germ-free housing had fewer progenitor cells and developed less dysplasia than in L2-IL1 mice raised under standard conditions; exposure of fecal microbiota from L2-IL1B mice fed the HFD to L2-IL1B mice fed the control diet accelerated tumor development.. In a mouse model of BE, we found that an HFD promoted dysplasia by altering the esophageal microenvironment and gut microbiome, thereby inducing inflammation and stem cell expansion, independent of obesity.

Topics: Adenocarcinoma; Adult; Aged; Animals; Barrett Esophagus; Carcinogenesis; Diet, High-Fat; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagus; Feces; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Obesity; Organoids; Serum; Time Factors; Tissue Culture Techniques

The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

Topics: Animals; Cells, Cultured; Centromere Protein A; Epidermis; Gene Expression Regulation; Gene Ontology; Humans; Inflammation Mediators; Interleukin-8; Keratinocytes; Leptin; Mice; Obesity; Signal Transduction; STAT3 Transcription Factor

To evaluate the effects of acute fish oil supplementation (FOS) in DNA damage, lymphocyte phenotype and cytokines production after strenuous exercise in obese individuals.. Sixteen sedentary obese (BMI >30.0 to <35.0 kg/m²) men performed two sessions of exhaustive exercise and consumed 2000 mg of either placebo or fish oil one hour before the exercise session; trials were separated by 14 days. Peripheral blood mononuclear cells were collected pre, immediately after and 1 h after both exercise sessions and stimulated in vitro with 2% phytohemagglutinin for cytokines secretion (IL-6, IL-8, TNF-α). Analysis of DNA damage index on total lymphocytes and the peripheral frequency of T helper CD4+ cells, T cytotoxic CD8+ cells, and CD19+ B cells were also performed.. FOS prevented the increase in serum cortisol levels and the production of TNF-α and IL-8 after strenuous exercise. The DNA damage index decreased 1 h after exercise in FOS trial. Moreover, a lymphocytosis, i.e. increases in the frequency of CD4+ and CD8+ T cells was observed immediately after exercise bout in both trials. Moreover, FOS prevented the decrease in CD8+ T cells below to baseline value 1 h after strenuous exercise.. Acute supplementation with fish oil attenuates the proinflammatory cytokine response and diminished the DNA damage after strenuous exercise in obese individuals, suggesting a possible protective effect against the exacerbation of systemic damage induced by exhaustive exercise in obese individuals.

Topics: Adult; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dietary Supplements; DNA Damage; Exercise; Fish Oils; Humans; Hydrocortisone; Inflammation; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Obesity; Tumor Necrosis Factor-alpha

Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients.

Topics: Aged; Body Mass Index; Cell Communication; Chondrocytes; Female; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; Models, Biological; Obesity; Osteoarthritis; Synovial Fluid; T-Lymphocyte Subsets

To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC).. Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture.. Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction. After 120 hours, there was a higher secretion of inflammatory cytokines IL-1β and IL-8. CD8. These results demonstrate that chronic systemic inflammation observed in obesity induces dysfunctional features in PBMC that are consistent with premature immunosenescence.

Topics: Adult; Apoptosis; CD8-Positive T-Lymphocytes; Culture Media; Female; Humans; Immunosenescence; Inflammation; Interleukin-1beta; Interleukin-8; Leukocytes, Mononuclear; Macrophages; Male; Obesity; Serum; Signal Transduction

Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models.. Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis.. We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency.. We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.

Topics: Adipose Tissue; Animals; Arthritis, Rheumatoid; Cell Movement; Chemokine CXCL2; Collagen; Cytokines; Dietary Fats; Disease Models, Animal; Interleukin-8; Joints; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neutrophils; Obesity; Signal Transduction; Toll-Like Receptor 4

There is a growinge body of evidence pointing towards an important role for Toll-like receptors (TLR) especially TLR4 in obesity and metabolic syndrome.. Owing to the paucity of data on the effect of the accessory proteins, lipopolysaccharide (LPS)-binding protein (LBP) and soluble CD14 (sCD14) on TLR4 activation, the present study was undertaken to examine the effect of sCD14 and LBP on TLR4 activation in pivotal cells of meta-inflammation, monocytes and adipocytes.. The dose-response effects of sCD14 and LBP on TLR4 protein abundance in monocytes obtained from normal human volunteers was determined by flow cytometry and in human-differentiated adipocytes by western blotting. Additionally, the nuclear factor-kappaB (NF-κB) p65 and downstream biomediators interleukin (IL)-1β, IL-8, IL-6 and tumor necrosis factor (TNF)-α were measured in the cell culture supernatants by ELISA (enzyme-linked immunosorbent assay).. In LPS-primed monocytes, sCD14 but not LBP, augments both TLR4 abundance and inflammatory biomediators (IL-1β, IL-8, IL-6 and TNF-α).sCD14 also showed a similar effect in LPS-primed human adipocytes by augmenting TLR4 protein expression and activity in terms of NF-κB p65 and downstream biomediators (IL-1β, IL-8, IL-6 and TNF-α). LBP at the highest concentration only promoted secretion of IL-8 and TNF-α. However in both monocytes and adipocytes, the effect of sCD14 was superior to LBP.. In the present report, we make the novel observation that sCD14 compared with LBP, offers a preferred target to ameliorate TLR especially TLR4-induced inflammation and insulin resistance in human obesity and metabolic syndrome.

Topics: Acute-Phase Proteins; Adipocytes; Carrier Proteins; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Membrane Glycoproteins; Metabolic Syndrome; Monocytes; NF-kappa B; Obesity; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression.

Topics: Actins; Adipocytes; Adipose Tissue, White; Adult; Aged; Aged, 80 and over; Animals; Cell Line, Tumor; Cell Movement; Chemokine CXCL1; Diet, High-Fat; Disease Progression; Endothelial Cells; Humans; Interleukin-8; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Neovascularization, Pathologic; Obesity; Primary Cell Culture; Prostatic Neoplasms; Receptors, Interleukin-8A; Receptors, Interleukin-8B; RNA, Small Interfering; Tissue Array Analysis; Tumor Microenvironment; Xenograft Model Antitumor Assays

Diabetes mellitus (DM) during pregnancy causes congenital malformation, macrosomia, respiratory distress syndrome, and other abnormalities in neonates, but whether maternal DM affects the neonatal innate immune system is unknown. Therefore we aimed to reveal the influence of DM in pregnancy on the toll-like receptor (TLR)-mediated innate immune response in neonates. Cord blood was collected after full-term vaginal or cesarean delivery and classified into a DM group (n=8) and non-DM (control) group (n=7). Mononuclear cells were harvested from cord blood by using density gradient centrifugation, after which anti-CD14 magnetic beads were used to isolate monocytes from the mononuclear population. After monocytes were cultured with lipopolysaccharide (TLR4 ligand), flagellin (TLR5 ligand), Pam3CSK4 (TLR1/TLR2 ligand), zymosan (TLR2/TLR6 ligand), or macrophage-activating lipopeptide (TLR2/TLR6 ligand) for 12h, the cytokine levels (interleukin [IL]-8, IL-6, IL-1β, IL-10, tumor necrosis factor alpha and IL-12) in the culture supernatants were measured. Compared with the control group, the DM group had higher concentrations of IL-8 (P=0.01) and tumor necrosis factor alpha (P=0.02) after monocyte cultures were stimulated with Pam3CSK4 and higher concentrations of IL-8 (P=0.01) after flagellin treatment. In contrast, stimulation with lipopolysaccharide, zymosan, or macrophage-activating lipopeptide did not lead to any difference in cytokine profiles between the two groups. These data indicate that maternal DM induces excessive inflammatory activation in neonates via a TLR5- or TLR1/2-mediated innate immune response.

Topics: Adult; Cells, Cultured; Escherichia coli Infections; Female; Humans; Immunity, Innate; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-8; Listeriosis; Monocytes; Obesity; Pregnancy; Pregnancy in Diabetics; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 5; Tumor Necrosis Factor-alpha

Obesity triggers complex inflammatory networks within the innate immune system. During pregnancy, the placenta amplifies the low-grade inflammation through activation of Toll-like receptor 4 (TLR4) signalling pathways. The purpose of this study was to investigate the impact of obesity on placental TLR4 expression and inflammatory signals. The secondary aim was to analyse the placental cell type responsible for TLR4 activation.. Thirty-nine women recruited at term-scheduled Caesarean section were grouped according to their pre-gravid BMI (<25 kg/m(2) and >30 kg/m(2)). Placenta, venous maternal and cord blood were obtained at delivery for analysis. Data were analysed with linear regression and Spearman's rank correlation coefficient analysis.. TLR4, IL6 and IL8 expression was increased three- to ninefold (p < 0.001) in the placenta of obese vs lean women. There was a positive correlation between placental TLR4 and maternal systemic and placental IL6 and IL8 concentrations. Placental TLR4 expression was correlated with maternal pre-gravid BMI, insulin resistance index, plasma insulin and C-reactive protein (r = 0.57, 0.31, 0.35, 0.53, respectively; p < 0.001) but not with plasma glucose, maternal age, gestational age and gestational weight gain (r < 0.2; p > 0.1). TLR4 was located in both trophoblast and macrovascular endothelial cells lining fetal vasculature. Lipopolysaccharide-induced TLR4 activation was more robust in trophoblasts than in endothelial vascular cells (100-fold vs tenfold; p < 0.001).. Trophoblastic TLR4 is strongly implicated in the propagation of placental inflammation. Placental inflammation is related to maternal metabolic conditions such as pre-gravid BMI, whilst gestational weight gain or gestational age are not. These results implicate the pre-gravid condition as a significant contributor to metabolic inflammation in late pregnancy.

Topics: C-Reactive Protein; Female; Gestational Age; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Obesity; Placenta; Pregnancy; Signal Transduction; Toll-Like Receptor 4

Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 ± 0.05 and 0.71 ± 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 ± 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 ± 0.06 OZR-C, 0.30 ± 0.05 OZR-WB, 0.29 ± 0.03 LZR-C, and 0.30 ± 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR (-37%) and LZR (-30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased (-31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function.

Topics: Adiponectin; Adipose Tissue, White; Animals; Aorta, Thoracic; Arteries; Biomarkers; Blueberry Plants; Chemokine CCL2; Endothelium, Vascular; Food, Preserved; Fruit; Interleukin-8; Obesity; Phenylephrine; Random Allocation; Rats, Zucker; Tumor Necrosis Factor-alpha; Vasculitis; Vasoconstriction; Vasoconstrictor Agents

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction.. Cross-sectional analysis of baseline investigations of a randomized controlled trial.. Clinic-based.. There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] ≥15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group.. None.. Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α were assessed in relation to OSA diagnosis based on AHI ≥ 15 events/h as well as oxygen desaturation index (ODI) ≥ 5 events/h.. Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI ≥ 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI ≥ 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis.. OSA with ODI ≥ 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Odds Ratio; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Topics: Asthma; Body Mass Index; Cell Count; Eosinophils; Forced Expiratory Volume; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Neutrophils; Obesity; Ozone; Retrospective Studies; Spirometry; Sputum; Vital Capacity

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists.

Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Body Mass Index; Cyclooxygenase 2; Female; Health Status; Health Surveys; Humans; Interleukin-1beta; Interleukin-8; Life Change Events; Male; Middle Aged; Obesity; Racial Groups; RNA; Sex Factors; Smoking; Socioeconomic Factors; Stress, Psychological

Obesity is considered a subchronic inflammatory disease with high risk of comorbidity development. Obesity-associated inflammation originates from adipose tissue itself, which secretes a panel of inflammatory chemokines and cytokines. Therefore, we enrolled 23 obese women without comorbidity and evaluated if simvastatin 20 mg/day dose therapy for 6 weeks (n=15) may modulate plasma levels of inflammatory CXCL-10, CCL-2, CXCL-9, CXCL-8, and CCL-5. A significant decrease of cholesterol and its fractions, triglycerides, and high-sensitivity C-reactive protein (hsCRP) after simvastatin treatment was observed when compared to placebo (n=8). Chemokine plasma levels were unchanged by statin intake when compared to placebo. Although dyslipidemia biomarkers and hsCRP have been diminished by simvastatin, low chemokine amounts produced by healthy obese women do not seem to be altered by simvastatin anti-inflammatory activity.

Topics: Adipose Tissue; Adult; Biomarkers; C-Reactive Protein; Chemokine CCL2; Chemokine CCL5; Chemokine CXCL10; Chemokine CXCL9; Chemokines; Cholesterol; Comorbidity; Female; Humans; Hypolipidemic Agents; Inflammation; Interleukin-8; Middle Aged; Obesity; Simvastatin; Triglycerides; Young Adult

Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD.. The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered.. Adolescents with pathological periodontal pockets (PD ≥ 4 mm; n = 14) had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets (PD ≥ 4 mm; n = 61). The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable "diastolic blood pressure". The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother's country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis.. In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.

Topics: Adolescent; Age Factors; Body Mass Index; Chemokine CCL2; Child; Cross-Sectional Studies; Dental Plaque Index; Diastole; Female; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Periodontal Index; Periodontal Pocket; Pilot Projects; Sex Factors; Systole; Thyrotropin

High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we investigated whether chemokines associated with obesity and prostatic inflammation can be measured in normally voided urine of BPH/LUTS patients to demonstrate the mechanistic association between obesity and BPH/LUTS.. Frozen urine specimens of BPH/LUTS patients enrolled in the Nashville Men's Health Study were sent for blinded analysis to University of Pittsburgh. Thirty patients were blocked by their AUA-SI (>7 or ≤7) and prostatic enlargement (<40, 40-60, >60 cc). Clinical parameters including age, prostate size, and medications were derived from chart review. CXC chemokines (CXCL-1, CXCL-8, and CXCL-10), CC chemokines (CCL2 and CCL3), and sIL-1ra were measured in thawed urine using Luminex™ xMAP(®) technology and ELISA for NGF.. Urinary CCL2 levels were several fold higher compared with the other six proteins, of which CCL3 was detectable in less than one-fourth of patients. Urine levels of sIL-1ra and CXCL-8 were significantly associated with increasing BMI and waist circumference in BPH patients. CXCL-8 showed a marginal association with overall AUA-SI scores, as well as obstructive (p = 0.08) symptom subscores. Prostate volume was inversely and marginally associated with urinary CXCL-10 (p = 0.09).. Urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with varying degrees with LUTS severity, prostate size, and obesity, respectively. These findings in urine are consistent with past studies of chemokine levels from expressed prostatic secretions and demonstrate the potential of noninvasively measured chemokine in urine to objectively classify BPH/LUTS patients.

Topics: Adult; Chemokine CXCL10; Humans; Inflammation; Interleukin-8; Lower Urinary Tract Symptoms; Male; Middle Aged; Obesity; Prostate; Prostatic Hyperplasia; Statistics as Topic; Urine Specimen Collection

In endometrial cancer, visceral obesity, as a risk factor, is associated with a chronic inflammatory process, confirmed by the elevation of serum inflammatory markers in obese patients. The aim of the present study was to evaluate the correlation between visceral fat, assessed by ultrasonography, and the systemic levels of interleukin (IL)-8 in patients with endometrial cancer. This study also evaluated the usefulness of abdominal ultrasonography in assessing the visceral fat correlated with systemic inflammatory status, as an alternative method to identify patients at risk of endometrial cancer.. The study was a case-control analysis including two groups of patients: Group I: 44 patients diagnosed with endometrial cancer; group II: 44 patients with no gynecological pathology. The diagnosis of endometrial cancer was performed following histopathological examination that evaluated the tissue material obtained through endometrial biopsy. These patients underwent ultrasound examination by which intraperitoneal fat was determined. IL-8 levels were determined for each patient. The Student's t-test was used for the comparison of the means and the Mann-Whitney test for rank comparison of two independent samples.. In patients diagnosed with endometrial cancer, the visceral fat area evaluated by ultrasound was significantly larger (p<0.0001) compared to that of the control group. The plasma levels of IL-8 in the endometrial cancer group were significantly elevated (p<0.001) compared to the control group. A positive linear correlation was also found between the visceral fat area and plasma levels of IL-8.. The plasma levels of IL-8 are positively linearly correlated with visceral fat. Determination of visceral fat in association with IL-8 levels may be a predictive factor for endometrial cancer.

Topics: Body Mass Index; Case-Control Studies; Endometrial Neoplasms; Female; Follow-Up Studies; Humans; Interleukin-8; Intra-Abdominal Fat; Middle Aged; Neoplasm Staging; Obesity; Prognosis; ROC Curve

The origin(s) of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the impact of exposure to ambient air pollution on systemic biomarkers of inflammation (C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-6, IL-8 and fibrinogen) and tissue repair (hepatocyte growth factor (HGF)) in 242 clinically stable COPD patients (mean age 67.8 years and forced expiratory volume in 1 s 71.3% predicted) in Barcelona, Spain, in 2004-2006. A spatiotemporal exposure assessment framework was applied to predict ambient nitrogen dioxide (NO2) and levels of particles with a 50% cut-off aerodynamic diameter of 2.5 μm (PM2.5) at each participant's home address during 10 periods of 24 h (lags 1-10) and 1 year prior to the blood sampling date. We used linear regression models to estimate associations between biomarkers and exposure levels. An interquartile range (IQR) increase in NO2 exposure in lag 5 was associated with 51%, 10% and 9% increases in CRP, fibrinogen and HGF levels respectively. We also observed 12% and 8% increases in IL-8 associated with an IQR increase in NO2 exposure in lag 3 and over the year before sampling, respectively. These increases were larger in former smokers. The results for PM2.5 were not conclusive. These results show that exposure to ambient NO2 increases systemic inflammation in COPD patients, especially in former smokers.

Topics: Aged; Air Movements; Air Pollutants; Air Pollution; Biomarkers; C-Reactive Protein; Cohort Studies; Female; Fibrinogen; Forced Expiratory Volume; Hepatocyte Growth Factor; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Nitrogen Dioxide; Obesity; Particulate Matter; Pulmonary Disease, Chronic Obstructive; Research Design; Smoking; Tumor Necrosis Factor-alpha

Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8). Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance.

Topics: Adipose Tissue; Animals; Blood Proteins; Blotting, Western; Body Mass Index; Cells, Cultured; Diet, High-Fat; Glucose Tolerance Test; Humans; Immunoenzyme Techniques; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Interleukin-6; Interleukin-8; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Proto-Oncogene Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation.. AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression.. Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive.. AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.

Topics: Age Factors; Aged; Amputation, Surgical; Arthroplasty, Replacement, Knee; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Comorbidity; Cytokines; Diabetes Mellitus; Elective Surgical Procedures; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Leptin; Linear Models; Male; Middle Aged; Obesity; Peripheral Vascular Diseases; Phenotype; Plasminogen Activator Inhibitor 1; Polypharmacy; Prospective Studies; Resistin; Sex Factors; Subcutaneous Fat

Obesity and hypertension have been recognized as inflammatory diseases capable of activating the immune system, thus contributing to an increased cardiovascular risk. However, the link between adaptive immunity, obesity, and hypertension is poorly understood. We investigated the relationship of the body mass index (BMI) on the inflammatory, vascular, and immune responses in patients with hypertension naïve of anti-hypertensive treatment. Hypertensive patients (N = 88) were divided into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects. Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB-D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were assessed. OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0.05), without differences between groups regarding anti-ApoB-D Abs. After adjusting for age, systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated with BMI and waist circumference (r = -0.24, P = 0.02 and r = -0.25, P = 0.02, respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0.22, P = 0.05 for systolic, and r = 0.29, P = 0.01 for diastolic blood pressure). Regression analyses showed inverse associations of anti-oxLDL Abs with BMI (β = -0.05, P = 0.01) and waist circumference (β = -0.01, P = 0.02); anti-ApoB-D Abs were associated with systolic and diastolic 24-h ABPM (β = 0.96, P = 0.04; β = 1.02, P = 0.005, for systolic and diastolic 24-h ABPM, respectively). Among hypertensive patients, obesity modulates the immune and inflammatory milieu, determining an unfavorable balance of cytokines and reduction in titers of anti-oxLDL Abs. Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.

Topics: Adult; Aged; Antihypertensive Agents; Apolipoproteins B; Apolipoproteins D; Autoantibodies; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Interleukin-10; Interleukin-8; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Monitoring, Ambulatory; Obesity

In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose.. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated.. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6).. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.

Topics: Adult; Asymptomatic Diseases; Blood Glucose; C-Reactive Protein; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Prediabetic State

Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer.. We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial "disease phenotype" affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny.. This was a prospective study conducted at an academic medical center.. Proliferative-phase endometrium was obtained from 6 overweight/obese PCOS (National Institutes of Health criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting-isolated endometrial epithelial cells (eEPs), endothelial cells, stromal fibroblasts (eSFs), and mesenchymal stem cells (eMSCs). Gene expression data were validated using microfluidic quantitative RT-PCR and immunohistochemistry.. The comparison between eEP(PCOS) and eEP(Ctrl) showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSF(PCOS) and eSF(Ctrl) showed up-regulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSC(PCOS) vs eMSC(Ctrl), the most up-regulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). Immunohistochemistry scoring showed increased expression of CCL2 in eEP(PCOS) and eSF(PCOS) compared with eEP(Ctrl) and eSF(Ctrl) and IL-6 in eEP(PCOS) compared with eEP(Ctrl).. Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and prooncogenic changes, independent of body mass index, especially in eEP(PCOS) and eMSC(PCOS), compared with controls. The study reveals an endometrial disease phenotype in women with PCOS with potential negative effects on endometrial function and long-term health.

Topics: Adult; Body Mass Index; Cell Proliferation; Endometrium; Female; Gene Expression; Humans; Inflammation; Interleukin-6; Interleukin-8; Mesenchymal Stem Cells; Obesity; Overweight; Polycystic Ovary Syndrome; Up-Regulation

Adipose tissue expansion during obesity is associated with a state of low-grade inflammation and an increase in macrophage infiltration, which predisposes to insulin resistance and vascular malfunction. Growing evidence suggests that vitamin D3 has immunoregulatory effects and adipose tissue could be a target for vitamin D3 action. Preadipocytes, one of the major cell types in adipose tissue, are actively involved in inflammatory processes.. This study investigated whether the active form of vitamin D3 (1,25(OH)2D3) affects the production of proinflammatory chemokines/cytokines and the monocyte recruitment by human preadipocytes.. The secretion levels of monocyte chemoattractant proteint-1 (MCP-1), IL-8 and IL-6 were significantly higher in preadipocytes than in differentiated adipocytes, suggesting that preadipocytes could be a major source of proinflammatory mediators. Cytokine profile analysis revealed that 1,25(OH)2D3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFκB signalling was shown by the upregulation of IκBα protein abundance by 1,25(OH)2D3 in preadipocytes. In addition, 1,25(OH)2D3 was able to decrease the migration of THP-1 monocytes. Treatment with proinflammatory stimuli, including macrophage-conditioned (MC) medium, TNFα and IL-1β, led to a marked increase in protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)2D3 (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, TNFα and IL-1β on MCP-1 expression and protein release, although the effect on stimulated release of IL-6 was less potent.. These results demonstrate that 1,25(OH)2D3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment.

Topics: Adipocytes; Adipose Tissue, White; Adult; Blotting, Western; Cell Differentiation; Chemokine CCL2; Cytokines; Female; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Interleukin-6; Interleukin-8; Monocytes; NF-kappa B; Obesity; Signal Transduction; Tumor Necrosis Factor-alpha; Vitamin D

In obesity, adipose tissue becomes a significant source of chemokines and inflammatory cytokines that are associated with chronic systemic low-grade inflammation and may lead to insulin resistance. Studies in children have mainly focused on inflammatory cytokines and there are limited data for chemokines in adolescents and young adults. We studied the relation of chemokines to cardiovascular (CV)-risk factors, insulin resistance and adipocytokines in 18-21-year-old individuals.. Cross-sectional data collected in a cohort originally enrolled at mean age 13, with data for the present study obtained from 252 examined at age 18.7±0.1 years.. Multiple linear regression models were used to analyze the associations among chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1β (MIP-1β), visfatin and interleukin-8 (IL-8)) and between chemokines and body mass index (BMI), glucose, lipids, blood pressure (BP), insulin resistance (euglycemic hyperinsulinemic clamp) and adipocytokines (IL-6, TNF-α and adiponectin).. Chemokine levels were significantly intercorrelated. Significant associations (P<0.05) with adjustment for age, race and sex included: MIP-1β with waist circumference and IL-6, IL-8 with systolic BP and visfatin with IL-6. No other significant relations were found between the chemokines and the other variables. Further adjustment for BMI did not alter these conclusions.. Considered in the context of prior studies in children and adults, these results suggest that in large part, the association between chemokines and CV risk or inflammatory factors does not appear to develop until adult life.

Topics: Adipokines; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Chemokine CCL4; Chemokines; Cross-Sectional Studies; Female; Glucose Clamp Technique; Humans; Inflammation; Insulin Resistance; Interleukin-6; Interleukin-8; Lipids; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Risk Factors; Tumor Necrosis Factor-alpha; United States; Young Adult

Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus.. Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of 24 osteoarthritis-related and 4 obesity-related genes in meniscus was assessed by quantitative real-time PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman's rank-order correlation. Hierarchical cluster dendrogram and heat map were generated to study inter-gene associations.. Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=-0.447), NFκB2 (r=-0.361), NFκBIA (r=-0.312), IκBA (r=-0.308), IL-8 (r=-0.305), ADAMTS-4 (r=-0.294), APLN (apelin) (r=-0.250) and IL-6 (r=-0.244). Similarly, BMI was negatively correlated with the expression of APLN (r=-0.328), ACAN (r=-0.268) and MMP-1 (r=-0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=-0.272). However, age had an independent effect on the expression on ADAMTS-4 (r=-0.253), MMP-1 (r=-0.399), IL-8 (r=-0.327), COL1A1 (r=-0.287), NFκBIA (r=-0.278), NFκB2 (r=-0.312) and IκBA (r=-0.299). The gene correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix-degrading enzymes, cytokines and chemokines, and obesity genes.. Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. Although the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlation analysis implicated a common role for strongly correlated genes. Although age-related variations in gene expression appear to be more relevant than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.

Topics: ADAM Proteins; ADAMTS4 Protein; Adolescent; Adult; Aged; Aging; Apelin; Body Mass Index; Cartilage, Articular; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; I-kappa B Proteins; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Matrix Metalloproteinase 1; Menisci, Tibial; Middle Aged; NF-kappa B p52 Subunit; NF-KappaB Inhibitor alpha; Obesity; Osteoarthritis; Procollagen N-Endopeptidase; Protein Array Analysis; Real-Time Polymerase Chain Reaction; Tibial Meniscus Injuries; United States

Calorie restriction-induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis. This effect of weight loss was not driven by changes of peroxisome proliferator-activated receptor γ sensitivity to rosiglitazone. Weight loss also enhanced the expression of adiponectin and leptin while reducing that of monocyte chemoattractant protein 1 and interleukin-8 by cultured adipocytes. Thus, the weight-reducing (DI) increased adipogenic capacity of preadipocytes and shifted their secretion toward lower inflammatory profile. Reprogramming of preadipocytes could represent an adaptation to weight loss leading to partial restoration of preobese adipose tissue traits and thus contribute to the improvement of metabolic status. However, enhanced adipogenesis could also contribute to the unwanted weight regain after initial weight loss.

Topics: Adipocytes; Adipogenesis; Adiponectin; Cells, Cultured; Chemokine CCL2; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leptin; Obesity; PPAR gamma; Rosiglitazone; Thiazolidinediones; Weight Loss

Obesity, type 2 diabetes, and HIV-associated lipodystrophy are associated with abnormalities in adipocyte growth and differentiation. In persons with these conditions, adipose depots contain increased numbers of macrophages, but the origins of these cells and their specific effects are uncertain. Peripheral blood mononuclear cells (PBMC)-derived monocytes, but not T cells, cocultured via transwells with primary subcutaneous preadipocytes, increased proliferation (approximately twofold) and reduced differentiation (~50%) of preadipocytes. Gene expression analyses in proliferating preadipocytes (i.e., prior to hormonal induction of terminal differentiation) revealed that monocytes down-regulated mRNA levels of CCAAT/enhancer binding protein, alpha (C/EBPα) and up-regulated mRNA levels of G0/G1 switch 2 (G0S2) message, genes important for the regulation of adipogenesis and the cell cycle. These data indicate that circulating peripheral blood monocytes can disrupt adipogenesis by interfering with a critical step in C/EBPα and G0S2 transcription required for preadipocytes to make the transition from proliferation to differentiation. Interactions between preadipocytes and monocytes also increased the inflammatory cytokines IL-6 and IL-8, as well as a novel chemotactic cytokine, CXCL1. Additionally, the levels of both IL-6 and CXCL1 were highest when preadipocytes and monocytes were cultured together, compared to each cell in culture alone. Such cross-talk amplifies the production of mediators of tissue inflammation.

Topics: Adipocytes; Adipose Tissue; Blotting, Western; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cell Proliferation; Chemokine CXCL1; Cytokines; Diabetes Mellitus, Type 2; HIV-Associated Lipodystrophy Syndrome; Humans; Interleukin-6; Interleukin-8; Monocytes; Obesity; Real-Time Polymerase Chain Reaction; RNA, Messenger

The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease that are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared with premenopausal women. We also wanted to determine whether these markers are reduced by stable weight loss in obese women.. Anthropometric data, blood samples and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass (GBP) surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated.. IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal vs premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal vs premenopausal women. Two years after GBP surgery, adipose expression of IL-8, tumour necrosis factor-α and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before GBP surgery, but these associations disappeared after surgery.. Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss.

Topics: Adipose Tissue; Adult; Aged; C-Reactive Protein; Chemokine CCL2; Female; Humans; Interleukin-6; Interleukin-8; Middle Aged; Obesity; Postmenopause; Premenopause; Real-Time Polymerase Chain Reaction; Young Adult

Obesity is a multifactorial disease resulting from interactions between susceptibility genes, psychosocial, and environmental factors. However, it is becoming evident that interindividual differences in obesity susceptibility depend also on epigenetic factors, although the mechanisms have not been fully elucidated. We have undertaken a genome-wide analysis of DNA methylation of human preadipocytes and mature adipocytes to examine the differences in methylation between them. We found hypomethylation occurring in 2,701 genes and hypermethylation in 1,070 genes after differentiation. Meanwhile, Gene Ontology analysis and Ingenuity Pathway Analysis showed many significant gene functions and pathways with altered methylation status after adipocyte differentiation. In addition, Signal-Net analysis showed that tumor necrosis factor-α, mitogen-activated protein kinase, and interleukin-8 were important to the formation of this network. Our results suggest that DNA methylation mechanisms may be involved in regulating the differentiation process of human preadipocytes.

Topics: Adipocytes; Cell Differentiation; DNA Methylation; Humans; Interleukin-8; Mitogen-Activated Protein Kinases; Obesity; Tumor Necrosis Factor-alpha

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.

Topics: Adiponectin; Arthritis, Rheumatoid; Cells, Cultured; Cyclooxygenase 2; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Joints; Matrix Metalloproteinases; NF-kappa B; Obesity; Osteoarthritis; Receptors, Adiponectin; Receptors, Interleukin-1; Synovial Fluid

Type 2 diabetes and obesity are associated with increased risk of site-specific cancers. We have investigated whether metabolic alterations at the level of adipose-derived differentiating cells may affect specific phenotypes of breast cancer cells.. Growth profiles of breast cancer cell lines were evaluated in co-cultures with differentiated adipocytes or their precursor cells and upon treatment with adipocyte conditioned media. Production and release of cytokines and growth factors were assessed by real-time RT-PCR and multiplex-based ELISA assays.. Co-cultures with either differentiated mouse 3T3-L1 or human mammary adipocytes increased viability of MCF-7 cells to a greater extent, when compared with their undifferentiated precursors. Adipocytes cultured in 25 mmol/l glucose were twofold more effective in promoting cell growth, compared with those grown in 5.5 mmol/l glucose, and activated mitogenic pathways in MCF-7 cells. Growth-promoting action was also enhanced when adipocytes were incubated in the presence of palmitate or oleate. Interestingly, 3T3-L1 and human adipocytes released higher amounts of keratinocyte-derived chemokine/IL-8, the protein 'regulated upon activation, normally T expressed, and secreted' (RANTES), and IGF-1, compared with their precursor cells. Their levels were reduced upon incubation with low glucose and enhanced by fatty acids. Moreover, both undifferentiated cells and differentiated adipocytes from obese individuals displayed about twofold higher IGF-1 release and MCF-7 cell growth induction than lean individuals. Finally, inhibition of the IGF-1 pathway almost completely prevented the growth-promoting effect of adipocytes on breast cancer cells.. IGF-1 release by adipocytes is regulated by glucose and fatty acids and may contribute to the control of cancer cell growth in obese individuals.

Topics: Adenocarcinoma; Adipocytes; Adult; Aged; Breast Neoplasms; Cell Communication; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemokine CCL5; Coculture Techniques; Female; Glucose; Humans; Insulin-Like Growth Factor I; Interleukin-8; MCF-7 Cells; Middle Aged; Obesity; Oleic Acid; Palmitates; Signal Transduction

Many inflammation parameters are associated with obesity, but few comparable data are found in youth. This study aims to characterize the differences in serum levels of 13 biochemical inflammatory markers between boys with increased BMI and boys with normal BMI, and examine the relationships between inflammation markers, skinfold thicknesses, and body composition.. The participants were 38 boys (BMI above 85th percentile) and 38 boys (normal BMI) at the age of 10-11 years. Measurements included BMI, 9 skinfold thicknesses, waist and hip circumferences, and total body and trunk fat mass and percentage as indices of obesity, fasting insulin, glucose, and serum concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor, and CRP.. Overweight boys (OWB) were taller and more frequently in puberty than normal-weight boys (NWB). Skinfold thicknesses and body composition parameters were higher in OWB. They had significantly higher serum IL-6, IL-8, IFN-γ, MCP-1, and CRP values compared to NWB.. Six of 13 measured biochemical markers were significantly increased in OWB, indicating that many low-grade inflammatory processes are already involved in the development of obesity in childhood.

Topics: Body Mass Index; C-Reactive Protein; Case-Control Studies; Chemokine CCL2; Child; Humans; Ideal Body Weight; Interferon-gamma; Interleukin-6; Interleukin-8; Male; Obesity; Overweight; Skinfold Thickness

Autophagy, an evolutionary conserved process aimed at recycling damaged organelles and protein aggregates in the cell, also modulates proinflammatory cytokine production in peripheral blood mononuclear cells. Because adipose tissue inflammation accompanied by elevated levels of proinflammatory cytokines is characteristic for the development of obesity, we hypothesized that modulation of autophagy alters adipose tissue inflammatory gene expression and secretion. We tested our hypothesis using ex vivo and in vivo studies of human and mouse adipose tissue. Levels of the autophagy marker LC3 were elevated in sc adipose tissue of obese vs. lean human subjects and positively correlated to both systemic insulin resistance and morphological characteristics of adipose tissue inflammation. Similarly, autophagic activity levels were increased in adipose tissue of obese and insulin resistant animals as compared with lean mice. Inhibition of autophagy by 3-methylalanine in human and mouse adipose tissue explants led to a significant increase in IL-1β, IL-6, and IL-8 mRNA expression and protein secretion. Noticeably, the enhancement in IL-1β, IL-6, and keratinocyte-derived chemoattractant (KC) by inhibition of autophagy was more robust in the presence of obesity. Similar results were obtained by blocking autophagy using small interfering RNA targeted to ATG7 in human Simpson-Golabi-Behmel syndrome adipocytes. Our results demonstrate that autophagy activity is up-regulated in the adipose tissue of obese individuals and inhibition of autophagy enhances proinflammatory gene expression both in adipocytes and adipose tissue explants. Autophagy may function to dampen inflammatory gene expression and thereby limit excessive inflammation in adipose tissue during obesity.

Topics: Adipose Tissue; Animals; Autophagy; Cytokines; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Mice; Microtubule-Associated Proteins; Obesity; RNA, Small Interfering; Up-Regulation

In a cross-sectional study design we test the hypothesis of whether obesity in adolescence is associated with periodontal risk indicators or disease.. Obese adolescents (n=52) and normal weight subjects (n=52) with a mean age of 14.5 years were clinically examined with respect to dental plaque, gingival inflammation, periodontal pockets and incipient alveolar bone loss. The subjects answered a questionnaire concerning medical conditions, oral hygiene habits, smoking habits and sociodemographic background. Body mass index (BMI) was calculated and adjusted for age and gender (BMI-SDS). Samples of gingival crevicular fluid (GCF) were analyzed for the levels of adiponectin, plasminogen activator inhibitor-1 (PAI-1), interleukin-1β (IL-β), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α).. Obese subjects exhibited more gingival inflammation (P<0.001) and more pathological periodontal pockets (>4 mm) (P<0.001) but not incipient alveolar bone loss compared with the normal weight subjects. Higher levels of IL-1β (P<0.001) and IL-8 (P=0.002) were measured in GCF from obese subjects compared with the controls. In a multivariate logistic regression analysis, adjusted BMI-SDS (P=0.03; Odds Ratio [OR]=1.87) was significantly associated with the occurrence of pathological periodontal pockets.. The study demonstrates an association between obesity and periodontal risk indicators in adolescents that in the long term may lead to oral morbidity. This result further strengthens obesity's negative effect on teenagers' periodontal health and highlights the importance of a close collaboration between dentists and pediatricians in the prevention and treatment of obesity.

Topics: Adiponectin; Adolescent; Alveolar Bone Loss; Analysis of Variance; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Child; Cross-Sectional Studies; Dental Plaque; Female; Gingival Crevicular Fluid; Gingivitis; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Logistic Models; Male; Obesity; Odds Ratio; Periodontal Diseases; Periodontal Pocket; Plasminogen Activator Inhibitor 1; Risk Assessment; Risk Factors; Surveys and Questionnaires; Sweden; Tumor Necrosis Factor-alpha

The typical nutritional plan in Ramadan may have beneficial influences on the inflammatory state, as well as on metabolic and anthropometric parameters. We aimed to investigate the effects of Ramadan fasting on biochemical and hematological parameters and cytokines in healthy and obese individuals.. This study was performed during the Ramadan holy month (September and October 2007). The study group consisted of 10 obese males and the control group consisted of 10 males with a normal body mass index (BMI), who were admitted to the Family Medicine Outpatient Clinic of Dicle University Medical Faculty in Diyarbakir, Turkey, and who indicated that they were going to fast throughout the entire month of Ramadan. Individuals with any acute or chronic disease or medication during the study were excluded. Height, weight, BMI, and waist and hip circumferences were measured. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), urea, creatinine, insulin, total protein, albumin, C-reactive protein (CRP), lactic dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and cytokine levels were evaluated.. The average age of the participants was 27.4 ± 5.2 years. Of the study group, 7 fulfilled the criteria of metabolic syndrome. Significant weight reduction, significant decrease in BMI, and significant decrease of homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were observed in study group; weight and BMI reduction were insignificant and no significant change was observed in FBG levels, but a significant increase was observed in HOMA-IR in the control group. Post-Ramadan systolic and diastolic blood pressure values, serum white blood cells (WBC) count, interleukin-2 (IL-2), IL-8, tumor necrosis factor-α (TNF-α, TG, and ALT levels were significantly lower in both groups compared to pre-Ramadan values.. Ramadan fasting has beneficial influences on the inflammatory state, as well as metabolic and anthropometric parameters.

Topics: Adult; Body Mass Index; Body Weight; C-Reactive Protein; Carboxylic Ester Hydrolases; Cholesterol, LDL; Cross-Sectional Studies; Fasting; Humans; Interleukin-2; Interleukin-8; Islam; Male; Metabolic Syndrome; Obesity; Religion; Triglycerides; Tumor Necrosis Factor-alpha

The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. We hypothesized that cardiovascular risk factors are associated with the activation status of the innate immune system. We therefore assessed the responsiveness of TLRs on circulating cells in two groups of patients with established atherosclerosis and related this to the presence of cardiovascular risk factors. TNF (tumour necrosis factor)-α release induced by TLR2 and TLR4 activation was measured in patients with established coronary [PCI (percutaneous coronary intervention) study, n=78] or carotid artery disease [CEA (carotid endarterectomy) study, n=104], by stimulating whole blood samples with lipopolysaccharide (TLR4 ligand) and Pam3CSK4 [tripalmitoylcysteinylseryl-(lysyl)4; TLR2 ligand]. As an early activation marker, CD11b expression was measured by flow cytometry on CD14+ cells. Obesity was the 'only' risk factor that correlated with the TLR response. In both studies, obese patients had significantly higher TNF-α levels after stimulation of TLR2 compared with non-obese patients [16.9 (7.7-49.4) compared with 7.5 (1.5-19.2) pg/ml (P=0.008) in coronary artery disease and 14.6 (8.1-28.4) compared with 9.5 (6.1-15.7) pg/ml (P=0.015) in carotid artery disease; values are medians (interquartile range)]. Similar results were obtained following TLR4 stimulation. The enhanced inflammatory state in obese patients was also confirmed by a significant increased expression of the activation marker CD11b on circulating monocytes. In conclusion, obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherosclerosis; Carotid Artery Diseases; CD11b Antigen; Cohort Studies; Coronary Artery Disease; Endarterectomy, Carotid; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Risk Factors; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Obesity is associated with a systemic, low-grade inflammatory state. Although the relationship between obesity and semen parameters or prostate diseases has been previously investigated, the association between body mass index (BMI), prostate inflammatory diseases and color- Doppler ultrasound (CDU) of the male genital tract (MGT) has been poorly studied.. To evaluate the association between BMI and CDU features of the MGT, signs and symptoms of prostate inflammation, semen parameters.. We studied 222 men seeking medical care for couple infertility. According to the World Health Organization classification, subjects were divided into 3 groups: normal weight (no.=131, BMI=18.5-24.9 kg/m2), overweight (no.=71, BMI=25.0-29.9 kg/m2), obese (no.=20, BMI≥30.0 kg/m2). All patients underwent simultaneous testosterone evaluation and seminal analysis, including interleukin 8 (sIL-8), along with scrotal and transrectal CDU, before and after ejaculation. Prostatitis symptoms were evaluated by National Institutes of Health- Chronic Prostatitis Symptom Index questionnaire.. After adjusting for age and testosterone levels, higher BMI was significantly related to higher prostate volume and several CDU features of the prostate, including macro-calcifications, inhomogeneity, higher arterial peak systolic velocity (the latter adjusted also for blood pressure), but not with abnormalities of testis, epididymis, seminal vesicles. Furthermore, higher BMI and BMI class were significantly related to higher sIL-8, a reliable surrogate marker of prostate inflammatory diseases, even after adjustment for age. Conversely, no associations among BMI, clinical symptoms of prostatitis or semen parameters were observed.. Subjects with higher BMI might develop CDU and biochemical signs suggestive of prostate inflammation, although not clinically overt.

Topics: Adolescent; Adult; Body Mass Index; Humans; Infertility; Interleukin-8; Male; Middle Aged; Obesity; Prostate; Prostatitis; Semen; Testosterone; Ultrasonography, Doppler, Color

The recurrent hypoxic stress that characterizes obstructive sleep apnea (OSA) seems to play a role in the increased adherence of neutrophils to endothelial cells as well as in the resulting migration of the former to the inflamed area. Intercellular adhesion molecule 1 (ICAM-1) and interleukin (IL)-8 are markers widely used in OSA studies to investigate inflammation. The aim of this study was to measure ICAM-1 and IL-8 levels in the breath condensate and in the plasma and inflammatory cells in the induced sputum of 12 obese OSA (OO) patients, 10 nonobese OSA (NOO) patients, 10 obese non-OSA (ONO) subjects, and 8 healthy subjects (HS) using a specific enzyme immunoassay (EIA) kit. A significant increase in both plasma and exhaled IL-8 and ICAM concentrations and percentage neutrophils was observed in the induced sputum of obese OSA patients, non-obese OSA patients, and obese non-OSA subjects compared with healthy subjects. However, although these inflammatory markers were found to follow an upward trend in obese OSA patients no difference was observed in both either non-obese OSA patients and obese non-OSA subjects. Finally, a significant positive correlation was found to occur among IL-8, ICAM-1, and sputum neutrophils, as well as across the apnea-hypopnoea index (AHI), TST 90%, body mass index (BMI), and neck circumference. The data obtained confirm the occurrence of an ICAM- and IL-8-mediated neutrophilic airway inflammation in both OSA and obese patients. The degree of inflammation, which seems to worsen in cases of comorbidity (OSA and obesity), is likely to be responsible for the increased risk of developing cardiovascular events observed in these subjects, and therefore, it deserves to be elucidated even more.

Topics: Adult; Aged; Asthma; Breath Tests; Cell Count; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Neutrophils; Obesity; Sleep Apnea, Obstructive; Sputum

Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by hyperinsulinemic-euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase-PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein (MIP), interleukin-8 (IL-8)). Fasting glucose related to VAT expression of TNFalpha, MIP, serum amyloid A (SAA), IL-1alpha, IL-1beta, IL-8, and IL-8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element-binding protein (CREBP), IL-1beta, and IL-8. Insulin action related inversely to VAT complement C3 expression only. There were depot-specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol-binding protein-4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.

Topics: Adipokines; Adult; Aged; Body Mass Index; Chemokine CCL3; Diabetes Mellitus, Type 2; Female; Gene Expression; Humans; Inflammation; Insulin Resistance; Interleukin-8; Intra-Abdominal Fat; Male; Middle Aged; Obesity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Subcutaneous Fat; Tumor Necrosis Factor-alpha; Waist Circumference

To estimate the relationship between different adipokines and proinflammatory mediators in amniotic fluid and maternal body mass index (BMI), calculated as weight (kg)/height (m)2.. Seventy pregnant women who underwent amniocentesis for clinical reasons at 15-20 weeks of gestation were divided into two groups according to their BMI: a control group with normal weight (BMI 20-24.9, n=35) and a case group (BMI 25 or higher, n=35). The two groups were further divided into two subgroups: overweight (BMI 25-29.9, n=22) or obese (BMI 30 or more, n=13). Comparisons of amniotic fluid cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-8, IL-10, monocyte chemoattractant protein-1, resistin, and leptin) and C-reactive protein (CRP) levels were performed. The relationships between variables and maternal BMI were also analyzed.. There were significant differences in amniotic fluid CRP and TNF-alpha levels among the studied groups: CRP, 0.018 (+/-0.010), 0.019 (+/-0.013), and 0.035 (+/-0.028) mg/dL (P=.007); and TNF-alpha, 3.98 (+/-1.63), 3.53 (+/-1.38), and 5.46 (+/-1.69) pg/mL (P=.003), for lean, overweight, and obese women, respectively. Both proinflammatory mediators increased in women with obesity compared with both overweight and normal women (P=.01 and P=.008 for CRP; P=.003 and P=.01 for TNF-alpha, respectively). There were significant correlations between maternal BMI and amniotic fluid CRP (r=0.396; P=.001), TNF-alpha (r=0.357; P=.003) and resistin (r=0.353; P=.003).. Amniotic fluid CRP and TNF-alpha levels are increased in obese women, and both are related to maternal BMI, which suggests in utero exposure to higher proinflammatory cytokines and mediators in fetuses of these women.. II.

Topics: Adult; Amniotic Fluid; Body Mass Index; C-Reactive Protein; Chemokine CCL2; Cytokines; Female; Humans; Interleukin-10; Interleukin-8; Leptin; Obesity; Overweight; Pregnancy; Pregnancy Trimester, Second; Resistin; Tumor Necrosis Factor-alpha

CD40L figures prominently in atherogenesis. Recent data demonstrate elevated levels of sCD40L in the serum of patients with the metabolic syndrome (MS). This study investigated the role of CD40L in pro-inflammatory gene expression and cellular differentiation in adipose tissue to obtain insight into mechanisms linking the MS with atherosclerosis. Human adipocytes and preadipocytes expressed CD40 but not CD40L. Stimulation with recombinant CD40L or membranes over-expressing CD40L induced a time- and dose-dependent expression of IL-6, MCP-1, IL-8, and PAI-1. Supernatants of CD40L-stimulated adipose cells activated endothelial cells, suggesting a systemic functional relevance of our findings. Neutralising antibodies against CD40L attenuated these effects substantially. Signalling studies revealed the involvement of mitogen-activated protein kinases and NFkB. Furthermore, stimulation with CD40L resulted in enhanced activation of C/EBPa and PPARg and promoted adipogenesis of preadipose cells in the presence and absence of standard adipogenic conditions. Finally, patients suffering from the metabolic syndrome with high levels of sCD40L also displayed high levels of IL-6, in line with the concept that CD40L may induce the expression of inflammatory cytokines in vivo in this population. Our data reveal potent metabolic functions of CD40L aside from its known pivotal pro-inflammatory role within plaques. Our data suggest that CD40L may mediate risk at the interface of metabolic and atherothrombotic disease.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Cardiovascular Diseases; Case-Control Studies; CCAAT-Enhancer-Binding Proteins; CD40 Antigens; CD40 Ligand; Chemokine CCL2; Culture Media, Conditioned; Endothelial Cells; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Metabolic Syndrome; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Obesity; Plasminogen Activator Inhibitor 1; PPAR gamma; Recombinant Proteins; RNA, Messenger; Signal Transduction; Time Factors

In adults, studies have shown that obesity is a chronic low-grade inflammatory state characterized by altered levels of cytokines. Studies in children have mainly focused on C-reactive protein and adiponectin, and there is limited data for other inflammatory markers in healthy weight and overweight children. The aim of this study was to measure IL-6, IL-8 and IL-10 levels in healthy normal weight and overweight children at 8 and 15 years.. 118 normal weight and overweight children (59 boys) from the Nepean longitudinal study were recruited at age 8 years and followed up at 15 years. Serum IL-6, IL-8 and IL-10 levels were measured at both time-points.. At 8 years, we found no significant differences in cytokine levels between normal weight and overweight (owt)/obese (ob) groups. However, at 15 years, owt/ob girls (n = 23) had higher levels of IL-6 (p = 0.04), IL-8 (p = 0.04) and IL-10 (p = 0.03) compared to normal weight girls (n = 36), even after adjustment for puberty; no differences were seen in boys.. The effects of obesity on IL-6, IL-8 and IL-10 levels vary with age and sex, with owt/ob girls at 15 years showing raised IL-6, IL-8 and IL-10 levels compared to healthy weight girls.

Topics: Adolescent; Age Factors; Child; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Longitudinal Studies; Male; Obesity; Puberty; Sex Factors

Type 2 diabetes and obesity are associated with an enhanced release of a number of adipocytokines. Hyperinsulinemia, frequently present in type 2 diabetes and obesity, might be one of the drivers of the enhanced production of adipocytokines. The aim of this study was to investigate the interstitial levels of cytokines in subcutaneous adipose tissue (SCAT) in response to hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD. Hyperinsulinemia induced an increase of monocyte chemoatractant protein (MCP-1) and IL-6 SCAT interstitial and plasma levels and elevated IL-8 levels in SCAT. The relative changes of IL-6 levels in the dialysate correlated with changes of IL-8 and MCP-1. The interstitial and plasma levels of IL-1β, IL-10, TNFα, and plasminogen activator inhibitor (PAI-1) remained unchanged in response to hyperinsulinemia. VLCD resulted in enhancement of the hyperinsulinemia-induced augmentation of MCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1β, IL-10, TNFα, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT.

Topics: Adult; Caloric Restriction; Chemokine CCL2; Chemokines; Cytokines; Female; Glucose Clamp Technique; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Interleukin-6; Interleukin-8; Microdialysis; Middle Aged; Obesity; Subcutaneous Fat

Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither.. CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology.. Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01).. Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.

Topics: Adiponectin; Adult; Aged; Biomarkers; Chemokine CCL2; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Interleukin-8; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Using multiplex technology, the authors investigated the laboratory and biologic variation of a panel of cytokines (interleukin (IL)-1a, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, interferon-inducible protein-10, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) over 18 months and their relations to cardiovascular disease risk factors, hormone therapy, and weight loss. Data were obtained from the Woman On the Move through Activity and Nutrition (WOMAN) Study, a randomized clinical trial investigating the effect of nonpharmacologic interventions on subclinical atherosclerosis among overweight, postmenopausal women in Pennsylvania. The present analysis (February 2002-August 2005) comprised 290 women aged 52-62 years (mean age = 57 years). Most of the cytokines were detectable in a majority of the samples, and the between-individual biologic variation was greater than the within-individual biologic and laboratory variation. There was little association between use of hormone therapy at baseline or change in hormone therapy by 18 months and cytokine levels. Weight loss was associated with a decrease in levels of IL-1 receptor antagonist, IL-6, and C-reactive protein. The results suggest that a wide panel of cytokines may be measured simultaneously from one sample. There is large unexplained variability in cytokine levels that is probably due to genetic-environmental associations.

Topics: Analysis of Variance; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Chemokine CXCL10; Cytokines; Estrogen Replacement Therapy; Female; Humans; Inflammation; Interleukin-1; Interleukin-10; Interleukin-1alpha; Interleukin-4; Interleukin-6; Interleukin-8; Linear Models; Middle Aged; Obesity; Pennsylvania; Postmenopause; Prospective Studies; Proteomics; Randomized Controlled Trials as Topic; Receptors, Interleukin-1; Risk Assessment; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Weight Loss; Women's Health

Nutrigenomics is a new application of omics technologies in nutritional science. Nutrigenomics aims to identify molecular markers of diet-related diseases and mechanisms of interindividual variability in response to food. The aim of this study was to evaluate peripheral blood mononuclear cells (PBMC) as a model system and readily available source of RNA to discern gene expression signatures in relation to personalized therapy of obesity. PBMC were collected from obese men before and after an 8-week low-calorie diet (LCD) to lose weight. Changes in gene expression before and after the LCD were initially screened using a DNA-microarray platform and validated by qRT-PCR. Global gene expression analysis identified 385 differentially expressed transcripts after the LCD. Further analyses showed a decrease in some specific oxidative stress and inflammation genes. Interestingly, expression of these genes was directly related to body weight, while a lower IL8 gene expression was associated with higher fat mass decrease. Collectively, these observations suggest that PBMCs are a suitable RNA source and model system to perform nutrigenomics studies related to obesity and development of personalized dietary treatments. IL8 gene expression warrant further research as a putative novel biomarker of changes in body fat percentage in response to an LCD.

Topics: Adult; Caloric Restriction; Gene Expression Profiling; Genetic Markers; Humans; Inflammation Mediators; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Nutrigenomics; Obesity; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Weight Loss

Adipose tissue (AT) had emerged as an endocrine organ and a key regulator of the metabolically triggered inflammation. The aims of this study were 1) to investigate the usefulness of a multiplexed bioassay in characterizing a panel of adipokines in subcutaneous (sc) microdialysate samples and 2) to determine whether lean and obese individuals differ in their interstitial adipokines levels following microdialysis (MD) probe insertion. Ultrafiltrating MD membranes were inserted in opposite sites of the sc abdominal AT of six lean (L) and six obese (OB) males at the beginning (M1) and during the last 120 min (M2) of the study. Interstitial and serum concentrations of adipokines were quantified using the Luminex technique and ELISA at 60-min intervals for 5 h. In comparison with L subjects, OB subjects exhibited elevated interstitial leptin (P < 0.001), IL-8 (P < 0.05), and IL-18 levels (P = 0.05), as well as higher serum concentrations of leptin (P < 0.0001), IL-6 (P < 0.0001), tumor necrosis factor-alpha (P < 0.001), IL-8 (P = 0.01) and interferon-gamma-inducible protein 10 (P < 0.05). In samples from the M1 membranes, leptin decreased and IL-1alpha, IL-18, and RANTES (regulated on activation, normal T-cell expressed and secreted) remained relatively stable, whereas IL-6, IL-8, and monocyte chemoattractant protein-1 significantly increased after the first hour (P < 0.0001 vs. baseline). Notably, either the magnitude of increase from the initial values or the time pattern of all the adipokines in M1 and M2 dialysates were similar between the groups. In conclusion, the current work provides valuable information on the optimal time frame to collect in situ AT microdialysate samples. Further studies are needed, however, to unravel the intricate interplay of cytokines in AT interstitial fluid.

Topics: Adipokines; Adult; Chemokine CCL2; Chemokine CCL5; Chemokine CXCL10; Circadian Rhythm; Humans; Interleukin-18; Interleukin-1alpha; Interleukin-6; Interleukin-8; Leptin; Male; Membranes, Artificial; Microdialysis; Middle Aged; Obesity; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.

Topics: Adipocytes; Atherosclerosis; Biopsy; Cells, Cultured; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucose; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lipolysis; Lipopolysaccharides; Mesenchymal Stem Cells; Obesity; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha

Several adipocytokines have been implicated in the pathogenesis non-alcoholic fatty liver disease (NAFLD).. To assess adipocytokines in NAFLD patients and controls.. A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations.. Serum TNF-alpha and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-alpha and IL-8 (P < 6.319e-08), and between IL-6 and IL-8 (P < 5.271e-15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD (P < 0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls (P < 0.02, P < 0.002 and P < 0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-alpha was associated with NAFLD (P < 0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin (P < 0.05). Multivariate analysis indicated that TNF-alpha was the only independent predictor of fibrosis in NASH (P < 0.0004).. These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.

Topics: Adipokines; Adiponectin; Adult; Aged; Biopsy; Blood Glucose; Case-Control Studies; Cohort Studies; Cytokines; Fasting; Fatty Liver; Female; Humans; Immunoenzyme Techniques; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Linear Models; Liver; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Tumor Necrosis Factor-alpha

Of late, inflammatory reactions have been considered to play an important part in the development of atherosclerosis. Acute-phase inflammatory reaction, being initially a protective response directed within the homeostasis system towards lesion repair, may by itself due to various factors favor the development of pathological processes. Considering the role played by inflammation in the development of atherosclerosis, and inflammatory activity in obesity and diabetes mellitus (DM), a range of common and interrelated elements of these processes may be marked out. These are acute phase proteins and cytokines. Insulinoresistance, being the common precursor of obesity and DM, plays the key role in vascular lesion. The use of cytokine activity index seems to be a promising method of revealing patients with high risk of atherosclerosis.

Topics: Aged; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interferon-gamma; Interleukin-6; Interleukin-8; Middle Aged; Obesity; Tumor Necrosis Factor-alpha

Type 2 diabetes is associated with decreased levels of the glycosphingolipid sulfatide, as well as a state of low-grade inflammation. Sulfatide is reported to have anti-inflammatory properties in other cell-types. In the present study, the effects of sulfatide on adipokine (adiponectin, TNF-alpha, IL-6, and IL-8) production in human adipose tissue (AT) was investigated in vitro. Isolated human adipocytes and AT cultures were incubated with sulfatide isolated from pig brain [sulfatide containing a variety of fatty acids or isoforms of sulfatide with defined, saturated fatty acids with 16 (C16:0) or 24 (C24:0) carbon atoms]. Adiponectin production was increased 50-80%, by all sulfatide preparations. Only the C16:0 isoform decreased TNF-alpha, IL-6, and IL-8 production 20-30%. The C16:0 sulfatide has been shown to activate potassium channels in beta-cells, and glibenclamide, an ATP-sensitive K+-(KATP) channel blocker, reversed the C16:0-induced decrement in stimulated TNF-alpha, IL-6, and IL-8 release in adipocytes. Glibenclamide on its own was without effect on the production of adiponectin, TNF-alpha, IL-6, and IL-8. In conclusion, this study shows that, sulfatide exerts anti-inflammatory effects in human adipocytes and AT in vitro. Accordingly, the reported low serum levels of sulfatide in patients with type 2 diabetes might be of importance in relation to the chronic low-grade inflammatory state found in this disease.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Animals; Cells, Cultured; Humans; Interleukin-6; Interleukin-8; Obesity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfoglycosphingolipids; Swine; Tumor Necrosis Factor-alpha; Women

The aim of this study was to compare the use of several biomarkers to identify obese children and adolescents with increased metabolic risk. One hundred sixty-two Caucasian obese children and adolescents (41% males, 9-18 years old) referred to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP), fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of obese children had the MS defined using World Health Organization-derived child specific criteria. MS subjects had significantly lower AD (p<0.01) and higher log-PAI-1 (p<0.001), uric acid (p<0.0001), and IL-18 (p<0.001). Subjects with AD levels

Topics: Adiponectin; Adolescent; Biomarkers; C-Reactive Protein; Child; Female; Humans; Insulin; Interleukin-8; Italy; Male; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1; Prevalence; Prognosis; Retrospective Studies; Risk Factors; Uric Acid

Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP).. A total of 100 subjects, 50 obese (BMI>or=25 kg/m2) and 50 who were not obese (BMI<25 kg/m2) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay.. The circulating levels of MCP-1 and IL-8 in the serum were significantly (P<0.05) higher in obese subjects (BMI>30 kg/m2) compared with those of nonobese controls (BMI<25 kg/m2). The levels of CRP were positively correlated with BMI (P<0.001) or waist circumference (P<0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, P<0.02; IL-8, P<0.01) and/or waist circumference (MCP-1, P<0.009; IL-8, P<0.03). The levels of MCP-1 were positively related to the levels of CRP (P<0.007) or interleukin-6 (IL-6) (P<0.0001), and negatively related to the levels of HDL-cholesterol (P<0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (P<0.02) or IL-8 (P<0.03) in obese subject.. Our data demonstrated that the circulating levels of MCP-1 and IL-8 are related to obesity-related parameters such as BMI, waist circumference, CRP, IL-6, HOMA and HDL-cholesterol. These findings suggest that the circulating MCP-1 and/or IL-8 may be a potential candidate linking obesity with obesity-related metabolic complications such as atherosclerosis and diabetes.

Topics: Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Chemokine CCL2; Cholesterol, HDL; Female; Humans; Interleukin-8; Male; Obesity; Waist-Hip Ratio

Swine containment facilities are often highly contaminated with organic dusts that often contain varying levels of endotoxins and other microbial products. This study was performed to evaluate the effect of obesity on the inflammatory response induced by chronic or acute exposure to swine confinement buildings (SCB).. Two separate studies were performed; Study I included 36 SCB long-time workers and a control group of 35 matched male hospital workers never exposed to SCB. In Study II, 14 naïve healthy young subjects (8 overweight and 6 lean) volunteered to be acutely exposed to a SCB environment for 5 hr. Markers of sub-clinical inflammation linked to obesity (C-reactive protein (CRP), interleukin 6 (IL-6)) or to active inflammation (soluble adhesion molecules, IL-8, TNF) were measured.. In the first study, positive correlations were found between girth circumference and serum levels of IL-6 (r = 0.57, P = 0.0003) and CRP (r = 0.62, P < 0.0001) in the control group. These correlations were however blunted or lost in the SCB workers group who showed positive correlations between girth circumference and soluble l-selectin (r = 0.34, P = 0.04), TNFalpha (r = 0.37, P = 0.03), ICAM-1 (r = 0.61, P < 0.0001). In the second study involving acute SCB exposure of naïve volunteers, no significant differences were observed between normal weight and overweight subjects for white blood cells, nasal lavage cell counts, and IL-8 levels. However, higher levels of CRP, TNF, and IL-6 were detected in overweight volunteers compared to those who were lean.. In pig farmers (Study I), environmentally induced chronic inflammation appears to blunt the sub-clinical inflammation linked to obesity, whereas in naïve volunteers of Study II, environmentally induced acute inflammation seems to have a potentiating effect on obesity-related inflammatory markers.

Topics: Administration, Inhalation; Adolescent; Adult; Air Pollutants, Occupational; Animal Husbandry; Animals; Biomarkers; C-Reactive Protein; Case-Control Studies; Dust; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; L-Selectin; Male; Middle Aged; Obesity; Occupational Exposure; Swine; Tumor Necrosis Factor-alpha

Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects.. Cross-sectional analysis in 124 African women.. Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA).. Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations.. Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.

Topics: Abdominal Fat; Adult; Aged; Anthropometry; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Cytokines; Female; Humans; Insulin; Insulin Resistance; Interleukin-18; Interleukin-6; Interleukin-8; Lipids; Middle Aged; Obesity; Regression Analysis; South Africa; Triglycerides

To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.. Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-alpha, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.. Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).. High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

Topics: Acute Disease; Adiposity; Adult; Body Mass Index; Disease Progression; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Pancreatitis; Prognosis; Severity of Illness Index; Sex Characteristics; Tumor Necrosis Factor-alpha

Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We have previously shown that adiponectin is a powerful inducer of proinflammatory cytokines production by macrophages. The reported anti-inflammatory effect of adiponectin may be due to the induction of macrophage tolerance to further adiponectin exposure or to other proinflammatory stimuli including the Toll-like receptor (TLR) 3 ligand polyI:C and the TLR4 ligand lipopolysaccharide (LPS). We now present additional data supporting the hypothesis that adiponectin is a strong proinflammatory adipokine. More specifically, we demonstrate that adiponectin induces IL-1beta and IL-8 from THP-1 macrophage cell line. The effect of adiponectin is not restricted to differentiated THP-1 macrophages but it is evident at lower levels in undifferentiated THP-1 monocytes promoting TNF-alpha, IL-6, and IL-8 production. Thus, its high levels in the circulation of lean subjects render their macrophages resistant to several proinflammatory stimuli including its own thus acting in effect as an anti-inflammatory agent. Lowering of its high levels, as a consequence of increased body mass index (BMI), renders macrophages sensitive to any proinflammatory insult.

Topics: Adiponectin; Cell Line; Cytokines; Dose-Response Relationship, Drug; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Macrophages; Metabolic Syndrome; Monocytes; Obesity; Tumor Necrosis Factor-alpha

The complex pathology of disease has sparked the development of novel protein expression profiling techniques that require validation in clinical settings. This study focuses on multiplexed analyses of adipocytokines and biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular disease.. Multiplexed immunoassays using fluorescent microspheres and the Luminex-100 system were performed on plasma from 80 obese patients (40 with the metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss. Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6 concentrations measured with multiplex panels from 3 different manufacturers were compared with results from commercial ELISAs. Detection limits and between- and within-run imprecision were determined for each analyte. Bland-Altman analysis was used to determine agreement between multiplexed immunoassays and ELISAs.. Correlation between the Luminex multiplexed assays and ELISAs was good for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision values for the multiplex method were generally <15%. Relative changes in plasma leptin and insulin concentrations after diet-induced weight loss were similar whether assessed by multiplex assay or ELISA.. Although this technology appears useful in clinical research studies, low assay sensitivity and poor correlations with conventional ELISA methods for some analytes with very low plasma concentrations should be considered when using the Luminex platform in clinical studies.

Topics: Adipose Tissue; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Cytokines; Female; Fluorescent Dyes; Humans; Immunoassay; Insulin; Interleukin-6; Interleukin-8; Leptin; Male; Metabolic Syndrome; Microspheres; Middle Aged; Obesity; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Obesity is associated with an increased risk for cardiovascular disease. Although it is known that white adipose tissue (WAT) produces numerous proinflammatory and proatherogenic cytokines and chemokines, it is unclear whether adipose-derived chemotactic signals affect the chronic inflammation in atherosclerosis.. Histological examination showed that perivascular WAT (pWAT) is in close proximity to vascular walls, particularly at sites that have a tendency to develop atherosclerosis. In rodents, the amount of pWAT is markedly increased by a high-fat diet. At a functional level, supernatant from subcutaneous and pWAT strongly induced the chemotaxis of peripheral blood leukocytes. The migration of granulocytes and monocytes was mostly mediated by interleukin-8 and monocyte chemoattractant protein-1, respectively, whereas both chemokines contributed to the migration of activated T cells. Moreover, pWAT produces these chemokines, as shown by immunohistochemistry and by explant culture. The accumulation of macrophages and T cells at the interface between pWAT and the adventitia of human atherosclerotic aortas may reflect this prochemotactic activity of pWAT.. Human pWAT has chemotactic properties through the secretion of different chemokines, and we propose that pWAT might contribute to the progression of obesity-associated atherosclerosis.

Topics: Adipose Tissue; Animals; Aorta; Atherosclerosis; Cells, Cultured; Chemokine CCL2; Chemotaxis, Leukocyte; Diet, Atherogenic; Dietary Fats; Granulocytes; Humans; Interleukin-8; Monocytes; Obesity; Rats; Rats, Wistar

Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss.. Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women.. Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-alpha, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity.. In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.

Topics: Adult; Anthropometry; Cytokines; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Mitral Valve; Obesity; Premenopause; Reference Values; Ventricular Function; Weight Loss

The purpose of this study was to examine the source of adipokines released by the visceral and sc adipose tissues of obese humans. Human adipose tissue incubated in primary culture for 48 h released more prostaglandin E(2), IL-8, and IL-6 than adiponectin, whereas the release of plasminogen activator inhibitor 1 and hepatocyte growth factor was less than that of adiponectin but greater than that of leptin. IL-10 and TNFalpha were released in amounts less than those of leptin, whereas vascular endothelial growth factor and IL1-beta were released in much lower amounts. The accumulation of adipokines was also examined in the three fractions (adipose tissue matrix, isolated stromovascular cells, and adipocytes) obtained by collagenase digestion of adipose tissue. Over 90% of the adipokine release by adipose tissue, except for adiponectin and leptin, could be attributed to nonfat cells. Visceral adipose tissue released greater amounts of vascular endothelial growth factor, IL-6, and plasminogen activator inhibitor 1 compared with abdominal sc tissue. The greatly enhanced total release of TNFalpha, IL-8, and IL-10 by adipose tissue from individuals with a body mass index of 45 compared with 32 was due to nonfat cells. Furthermore, most of the adipokine release by the nonfat cells of adipose tissue was due to cells retained in the tissue matrix after collagenase digestion.

Topics: Abdomen; Adipocytes; Adiponectin; Adipose Tissue; Body Mass Index; Culture Techniques; Dinoprostone; Hepatocyte Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Kinetics; Leptin; Obesity; Plasminogen Activator Inhibitor 1; Proteins; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Viscera

To study the role of IL-8 in predicting future coronary artery disease (CAD) in apparently healthy men and women.. A nested case-control study was performed in the prospective EPIC-Norfolk population study. We measured baseline IL-8 concentrations among 785 apparently healthy individuals in whom fatal or nonfatal CAD developed during follow-up and 1570 matched controls. Baseline IL-8 concentrations were higher in cases than in matched controls (3.5 pg/mL versus 3.1 pg/mL, P=0.001). The risk of future CAD increased with increasing quartiles of IL-8 (P linearity <0.0001). Among individuals in the highest IL-8 quartile, the unadjusted odds ratio for future CAD was 1.72 (95% CI, 1.34 to 2.21; P<0.0001). The odds ratio for future CAD was still significant after adjustment for traditional risk factors (OR, 1.58; 95%CI, 1.19 to 2.09; P=0.002) and after additional adjustment for C-reactive protein and white cell count (OR, 1.77; 95% CI, 1.21 to 2.60; P=0.001).. We conclude that among apparently healthy men and women, elevated levels of IL-8 are associated with an increased risk of future CAD. These prospective data support a role for IL-8 in the development of CAD events.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Comorbidity; Coronary Disease; England; Female; Humans; Hypertension; Interleukin-8; Interleukins; Leukocyte Count; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Odds Ratio; Predictive Value of Tests; Prospective Studies; Risk; Risk Factors; Smoking; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the relationship between body mass index (BMI kg/m2), the inflammatory mediator tumor necrosis factor alpha (TNFalpha), and interleukin-8 (-8) in gingival crevicular fluid (GCF) from 32 obese subjects aged between 13 and 24 years. Gingival inflammation (GBI %), pathological pocket depths, and alveolar bone loss diagnosed on radiographs were recorded. The GCF was collected from six sites per subject using periopaper, and the volume was determined using Peritron 8000. The levels of TNFalpha and IL-8 were determined using ELISA kits. Within the whole group, there was no significant relationship between BMI and the variables age, GBI %, number of periodontal pockets, smoking, and the levels of TNFalpha or IL-8. In subjects with BMI > or =40, however, there was a statistically significant correlation (r= 0.74, P< 0.01) between the level of TNFalpha in GCF and BMI. The correlation coefficient between BMI and TNFalpha in subjects with BMI > or =40 differed significantly (P< 0.05) compared to that between subjects with BMI <40. The level of TNFalpha in GCF was positively correlated (P< 0.05) with BMI in subjects with no periodontal pathological pocket. No significant correlation was found between the level of IL-8 and BMI. The results indicate that BMI positively correlates with TNFalpha in GCF in the group of young subjects with BMI > or =40 as well as in the subjects with no pathological periodontal pocket (> or =4 mm) and that TNFalpha in GCF may be affected by the obese condition through a systemic effect.

Topics: Adolescent; Adult; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Gingival Crevicular Fluid; Humans; Interleukin-8; Male; Obesity; Periodontal Index; Periodontal Pocket; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

To study the association between anthropometric and metabolic parameters as well as the effect of weight loss on plasma levels of the adipose tissue-derived cytokines interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in abdominal obese men.. Nineteen obese (mean body mass index (BMI): 38.6+/-0.6 kg/m(2)) and ten lean men (mean BMI: 23.4+/-0.4 kg/m(2)) were included in the study. The obese subjects received a 4.2 MJ/day diet for 8 weeks, followed by 8 weeks on energy restriction (6.2 MJ/day) and 8 weeks on a weight-maintenance diet.. A dual energy X-ray absorptiometry (DEXA)-scan was performed to estimate body composition. Plasma levels of IL-8, IL-6 and TNF-alpha were measured by a specific ELISA method. Insulin sensitivity was assessed by the homeostasis model assessment method (HOMA).. Plasma levels of IL-8 and IL-6 were 30-40% higher in obese as compared with lean subjects (P<0.05), whereas no group difference in TNF-alpha was observed. During the intervention, obese subjects obtained a 30% reduction in fat mass (P<0.001), fasting insulin (P<0.05) and HOMA (P<0.05). Plasma levels of TNF-alpha and IL-6 were decreased by 25-30% (P<0.001) but IL-8 was increased by 30% (P<0.001) after weight loss. IL-8 and IL-6 were correlated with measures of insulin resistance, and changes in IL-6 but not IL-8 were correlated with the improvement in insulin sensitivity after weight loss.. Plasma levels of IL-8 and IL-6 were found to be increased and were correlated with measures of insulin resistance in abdominal obese male subjects. Weight loss was associated with changes in the circulating levels of IL-8, IL-6 and TNF-alpha indicating that these cytokines are influenced by weight loss.

Topics: Adult; Anthropometry; Humans; Insulin Resistance; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Thinness; Tumor Necrosis Factor-alpha; Weight Loss

Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-alpha). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-alpha on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% (P < 0.05) increase in plasma adiponectin and a 45% (P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% (P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-alpha (P < 0.01) and IL-6 plus its soluble receptor (P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.

Topics: Adiponectin; Adipose Tissue; Cytokines; Female; Gene Expression; Humans; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Male; Obesity; Proteins; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Loss

According to increasing experimental and clinical evidence the inflammatory processes take important part in the development of atherosclerosis and its complications. The aim of the study was to evaluate the concentrations of selected inflammatory (IL-6, IL-8, MCP-1 and TNF-alpha) and antiinflammatory (IL-10) cytokines in children and adolescents with atherosclerosis risk factors: obesity, hypertension and diabetes. We studied 64 children and adolescents aged 14.88 +/- 2.4 years. Children were divided into: group with obesity (n = 11), group with obesity accompanying by hypertension (n = 14), children with hypertension (n = 11) and diabetic group (n = 28). Control group consisted of 15 healthy children aged 15.3 yrs. The evaluation of studied cytokines was performed with the use of immunoenzymatic ELISA kits (R&D Systems). IL-6 concentration in the whole group was 5.7 +/- 19 pg/mL and was significantly higher than in controls--2.3 +/- 2.3 pg/mL (p = 0.04). The highest IL-6 level was found in obesity group--11 +/- 30 pg/mL (p = 0.02). Significant difference was also found in the group with obesity and hypertension--8.3 +/- 15 pg/mL (p = 0.046) and in diabetic children--6.5 +/- 14 pg/ml (0.046). Interleukin 8 level in whole group was 486 +/- 839 pg/mL and was not different from the control group--236 +/- 197 pg/mL. IL-10 level in the study group was 4.9 +/- 3 pg/mL and did not differ from controls--4.5 +/- 1.2 pg/mL. TNF-alpha level was significantly higher in whole study group--8.9 +/- 2.4 pg/mL (p = 0.04) compared to controls--8.0 +/- 4.9 pg/mL, and in children with obesity--9.5 +/- 1.5 pg/mL (p = 0.034) as well as in children with obesity and hypertension--9.6 +/- 3.1 pg/mL (p = 0.042). MCP-1 level did not differ between the studied groups (228 +/- 124 pg/mL in whole study group) and controls--182 +/- 46 pg/mL. Correlation analysis by Spearman showed significantly correlation between IL-6 and body mass index in the whole study group. TNF-alpha also correlated with body mass index.. Children and adolescents with obesity, obesity accompanying by hypertension and diabetes have elevated levels of IL-6 and TNF-alpha. IL-6 and TNF-alpha correlates with body mass index not only in obese but also in hypertensive, slim children. The elevated levels of cytokines (IL-6, TNF-alpha) in children with atherosclerosis risk factors (particularly obesity) can confirm the presence of inflammatory process in early phases of atherosclerosis.

Topics: Adolescent; Body Mass Index; Case-Control Studies; Chemokine CCL2; Child; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Interleukin-10; Interleukin-6; Interleukin-8; Male; Obesity; Risk Factors; Tumor Necrosis Factor-alpha

Obesity is associated with the increased risk of cardiovascular disease; however, mechanisms responsible for such an increase are not fully understood. IL-8 is a cytokine that might have atherogenic properties. Recent in vitro studies revealed that IL-8 is produced and secreted by human adipocytes. The aim of the present study was to evaluate plasma IL-8 concentrations in obese subjects and the relationships between circulating IL-8 and anthropometric and biochemical parameters and TNF-alpha system. A total of 75 subjects with normal glucose tolerance, 35 lean and 40 obese, were recruited for this study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test and after the euglycemic hyperinsulinemic clamp. A significant increase in plasma IL-8 was observed in the obese group. In simple regression analysis, performed for the initial evaluation of relationships, plasma IL-8 was related to body mass index, percentage of body fat, fat mass (FM), and soluble TNF-alpha receptor 2 (sTNFR2) in both groups and with waist-to-hip ratio and sTNFR1 in the obese. In multiple regression analysis, FM, waist-to-hip ratio, gender, sTNFR2, and low density lipoprotein cholesterol were responsible for 44% of IL-8 variability. During oral glucose tolerance testing, mean plasma IL-8 concentrations increased in both groups, whereas clamp resulted in a significant increase in plasma IL-8 only in the obese. We conclude that plasma IL-8 levels are increased in obese subjects, and are related to FM and TNF-alpha system. Increase in circulating IL-8 might be one of the factors linking obesity with greater cardiovascular risk.

Topics: Adipose Tissue; Adult; Antigens, CD; Body Composition; Body Constitution; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Interleukin-8; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Risk Factors; Sex Characteristics; Tumor Necrosis Factor-alpha

To obtain more information on the possible influence of body mass index (BMI) and weight loss on interleukin-8 (IL-8) in plasma and in the adipose tissue. Tumor necrosis factor-alpha (TNF-alpha) was used for comparison and determined in parallel with IL-8.. The study was divided into three parts: 1) a cross-sectional study that included 89 subjects; 2) a 20-week intervention study in which 34 healthy obese subjects received a dietary intervention for 8 weeks followed by an additional 12 weeks on a weight-stabilization diet; 3) from this latter study, a subgroup of 8 obese subjects was investigated with a subcutaneous adipose-tissue biopsy.. In the cross-sectional study, plasma levels of TNF-alpha (p < 0.01), but not IL-8, was correlated with BMI. However, in a subgroup (BMI, 20 to 30 kg/m(2)), IL-8 was correlated with BMI (p < 0.01). In the intervention study, weight loss and weight maintenance led to an increase in IL-8 by 30% (p < 0.05) and a decrease in TNF-alpha by 40% (p < 0.001), which were paralleled in the adipose tissue, demonstrating a 2- to 3-fold increase (p < 0.01) and a 40% to 80% decrease (p < 0.01) in IL-8 and TNF-alpha, respectively.. Weight loss in obese subjects was associated with opposite changes in the secretion and transcription of IL-8 and TNF-alpha in the adipose tissue, as well as in plasma. This could indicate that plasma IL-8 under some conditions may be related to changes in adipose tissue IL-8 production.

Topics: Adipose Tissue; Adult; Biopsy; Body Mass Index; Cross-Sectional Studies; Culture Techniques; Female; Gene Expression Regulation; Humans; Insulin; Interleukin-8; Leptin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Loss