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      Serum IL-12 Is Increased in Mexican Obese Subjects and Associated with Low-Grade Inflammation and Obesity-Related Parameters

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          Abstract

          Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF- α ), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index ( r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity ( r = 0.4481), body fat percentage ( r = 0.5625), serum glucose ( r = 0.3158), triglyceride ( r = 0.3714), and TNF- α ( r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans.

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          Most cited references27

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          The link between abdominal obesity, metabolic syndrome and cardiovascular disease.

          The prevalence of metabolic syndrome has increased dramatically in recent years, and the cluster of metabolic abnormalities it encompasses results in increased cardiovascular morbidity and mortality. The role of abdominal (visceral) obesity and the underlying molecular and cellular mechanisms central to this association have been the subject of intensive research in recent times. The aim of this review is to correlate data in this area, highlighting the central role of excess visceral fat and its secreted adipokines, and to review existing and emerging therapies. Data were generated from a search of the PubMed database using the terms 'abdominal obesity', 'metabolic syndrome', 'insulin resistance', 'adipokines', 'interleukin-6 (IL-6)', 'adiponectin', 'tumour necrosis factor-alpha (TNF-alpha)' and 'cardiovascular disease'. Metabolic syndrome is associated with a pro-inflammatory state, and the role of visceral obesity is thought to be central to this. Visceral obesity leads to alteration of the normal physiological balance of adipokines, insulin resistance, endothelial dysfunction and a pro-atherogenic state. In association with this, the presence of conventional cardiovascular risk factors such as hypertension, dyslipidaemia and smoking results in a significantly elevated cardiovascular and metabolic (cardiometabolic) risk. Better understanding of the molecular mechanisms central to this association has led to the development of potential therapeutic agents.
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            Insulin resistance associated to obesity: the link TNF-alpha.

            Adipose tissue secretes proteins which may influence insulin sensitivity. Among them, tumour necrosis factor (TNF)-alpha has been proposed as a link between obesity and insulin resistance because TNF-alpha is overexpressed in adipose tissue from obese animals and humans, and obese mice lacking either TNF-alpha or its receptor show protection against developing insulin resistance. The activation of proinflammatory pathways after exposure to TNF-alpha induces a state of insulin resistance in terms of glucose uptake in myocytes and adipocytes that impair insulin signalling at the level of the insulin receptor substrate (IRS) proteins. The mechanism found in brown adipocytes involves Ser phosphorylation of IRS-2 mediated by TNF-alpha activation of MAPKs. The Ser307 residue in IRS-1 has been identified as a site for the inhibitory effects of TNF-alpha in myotubes, with p38 mitogen-activated protein kinase (MAPK) and inhibitor kB kinase being involved in the phosphorylation of this residue. Moreover, up-regulation of protein-tyrosine phosphatase (PTP)1B expression was recently found in cells and animals treated with TNF-alpha. PTP1B acts as a physiological negative regulator of insulin signalling by dephosphorylating the phosphotyrosine residues of the insulin receptor and IRS-1, and PTP1B expression is increased in peripheral tissues from obese and diabetic humans and rodents. Accordingly, down-regulation of PTP1B activity by treatment with pharmacological agonists of nuclear receptors restores insulin sensitivity in the presence of TNF-alpha. Furthermore, mice and cells deficient in PTP1B are protected against insulin resistance induced by this cytokine. In conclusion, the absence or inhibition of PTP1B in insulin-target tissues could confer protection against insulin resistance induced by cytokines.
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              Leptin and Inflammation.

              The past few years of research on leptin have provided important information on the link between metabolism and immune homeostasis. Adipocytes influence not only the endocrine system but also the immune response through several cytokine-like mediators known as adipokines, which include leptin. It is widely accepted that leptin can directly link nutritional status and pro-inflammatory T helper 1 immune responses, and that a decrease of leptin plasma concentration during food deprivation can lead to an impaired immune function. Additionally, several studies have implicated leptin in the pathogenesis of chronic inflammation, and the elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, type II diabetes, or degenerative disease including autoimmunity and cancer. Conversely, reduced levels of leptin such as those found in malnourished individuals have been linked to increased risk of infection and reduced cell-mediated immune responses. We discuss here the functional influences of leptin in the physiopathology of inflammation, and the effects of leptin in the modulation of such responses.
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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2013
                20 February 2013
                : 2013
                : 967067
                Affiliations
                1Unidad de Medicina Experimental, Hospital General de México “Dr. Eduardo Liceaga”, México D. F. 06726, Mexico
                2Laboratorio de Hígado, Páncreas y Motilidad, Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México “Dr. Eduardo Liceaga”, México D. F. 06726, Mexico
                3Departamento de Biología de la Reproducción y Clínica de Desórdenes de Sueño, Universidad Autónoma Metropolitana-Iztapalapa, México D. F. 09340, Mexico
                4Servicio de Medicina Interna, Hospital General de México, México D. F. 06726, Mexico
                5Servicio de Banco de Sangre, Hospital General de México, México D. F. 06726, Mexico
                6Fundación Mexicana para la Salud, México D. F. 14610, Mexico
                7Servicio de Cirugía General, Hospital General de México “Dr. Eduardo Liceaga”, México, 06726 DF, Mexico
                8Unidad de Desarrollo Biomédico, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada 22860, Baja California, Mexico
                Author notes

                Academic Editor: Peter Plomgaard

                Article
                10.1155/2013/967067
                3590791
                23533314
                e9d7aae5-d282-4905-a7aa-7541fbef0ee2
                Copyright © 2013 K. Suárez-Álvarez et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 November 2012
                : 8 January 2013
                : 9 January 2013
                Categories
                Clinical Study

                Immunology
                Immunology

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