Barbarroja Puerto, NuriaLópez-Pedrera, CharyGarrido-Sánchez, LourdesMayas Torres, María DoloresOliva-Olivera, WilfredoBernal-López, María RosaEl Bekay, RajaaTinahones, Francisco J2013-02-132013-02-132012-10-24Barbarroja Puerto N, López-Pedrera C, Garrido-Sánchez L, Mayas Torres MD, Oliva-Olivera W, Bernal-López MR, et al. Progression from high insulin resistance to type 2 diabetes does not entail additional visceral adipose tissue inflammation. PLoS ONE. 2012; 7(10):e48155http://hdl.handle.net/10668/768Journal Article;Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.enInflamaciónResistencia a la InsulinaObesidad MórbidaDiabetes Mellitus Tipo 2Grasa IntraabdominalFN-kappa BInterleucina-1betaInterleucina-6LípidosARN MensajeroProteína Quinasa 1 Activada por MitógenosQuinasa Activada por Mitógeno 3Quinasas MAP Reguladas por Señal ExtracelularFactor de Transcripción STAT3Factor de Necrosis Tumoral alfaHumanosMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin ResistanceMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Obesity, MorbidMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Abdominal Fat::Intra-Abdominal FatMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::NF-kappa BMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1::Interleukin-1betaMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6Medical Subject Headings::Chemicals and Drugs::LipidsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Proline-Directed Protein Kinases::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP Kinases::Mitogen-Activated Protein Kinase 1Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP Kinases::Mitogen-Activated Protein Kinase 3Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP KinasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::STAT Transcription Factors::STAT3 Transcription FactorMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Monokines::Tumor Necrosis Factor-alphaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humansresearch article23110196open access10.1371/journal.pone.00481551932-6203PMC3480488