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      Relación del polimorfismo rs9939609 del gen FTO con factores de riesgo cardiovascular y niveles de adipocitoquinas en pacientes con obesidad mórbida Translated title: Relation of the rs9939609 gene variant in FTO with cardiovascular risk factor and serum adipokine levels in morbid obese patients

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          Abstract

          Introducción: Algunos polimorfismos del gen asociado con la masa grasa y la obesidad (FTO) se han relacionado con la obesidad y parámetros bioquímicos. Nuestro objetivo fue analizar la relación del polimorfismo rs9939609 del gen FTO con el peso corporal, factores de riesgo cardiovascular y los niveles séricos de adipocitoquinas en una muestra de pacientes con obesidad mórbida. Material y métodos: Una muestra de 129 pacientes con obesidad mórbida (IMC > 40) se analizó en un diseño de corte transversal. A todos los pacientes se les determinó el peso, presión arterial, glucemia basal, proteína C reactiva (PCR), insulina, resistencia a la insulina (HOMA-R), colesterol total, LDL-colesterol, HDL-colesterol, triglicéridos y adipocitoquinas (adiponectina leptina, resistina, TNF-alfa, y los niveles de interleucina-6). Se evaluó la masa grasa mediante bioimpedancia tetrapolar y registró prospectivamente la ingesta de nutrientes durante tres días. En todos ellos se genotipo el polimorfismo del gen FTO (rs9939609). Resultados: Cuarenta y un pacientes (31,8%) tenían el genotipo TT (grupo genotipo salvaje), 55 pacientes (42,6%) el genotipo TA y 33 pacientes (25,6%) el genotipo AA. El índice de masa corporal (43,6 (2,6) kg/m² vs. 44,1 (2,9) kg/m²; p < 0,05), masa grasa (52,0 (12,5) kg vs. 56,3 (11,7) kg: p < 0,05), el peso (111,6 (16,2) kg vs. 114,9 (18,9) kg; p < 0,05), niveles de proteína C reactiva (6,1(4,3) mg/dl vs. 9,8 (7,1) mg/dl; p < 0,05) y niveles de leptina (65,9 (52,2) ng/ml vs. 110,9 (74,1); < 0,05) fueron estadísticamente mayores en los pacientes que presentaron el alelo mutado (A). Conclusiones: El polimorfismo del gen FTO, rs9939609, se asocia con un mayor peso, masa grasa y niveles circulantes de leptina y proteína C reactiva en pacientes con obesidad mórbida.

          Translated abstract

          Background: Common polymorphisms of the fat mass and obesity associated gene (FTO) have been linked to obesity in some populations. The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels in morbid obese patients. Material and methods: A sample of 129 patients with obesity was analyzed in a cross sectional design. Weight, blood pressure, basal glucose, creactive protein (CRP), insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adipocytokines (leptin, adiponectin, resistin, TNF alpha, and interleukin 6) levels were measured. A tetrapolar bioimpedance and a prospective serial assessment of nutritional intake with 3 days written food records were realized. Genotype of FTO gene polymorphism (rs9939609) was studied. Results: Forty three patients (31.8%) had TT genotype, 55 patients (42.6%) TA genotype and 33 patients (25.6%) AA genotype. Body mass index (43.6 (2.6) kg/m² vs. 44.1 (2.9) kg/m²; p < 0.05), fat mass (52.0 (12.5) kg vs. 56.3 (11.7) kg: p < 0.05), weight (111.6 (16.2) kg vs. 114.9 (18.9) kg; p < 0.05), levels of C reactive protein (6.1 (4.3) mg/dl vs. 9.8 (7.1) mg/dl; p < 0.05) and levels of leptin (65.9 (52.2) ng/ml vs. 110.9 (74.1); < 0.05) were higher in mutant type group (A allele) than wild genotype group (TT). Conclusion: The FTO gene polymorphism, rs9939609, was found to be associated with weight, fat mass, C reactive protein and leptin levels in morbid obese patients with A allele.

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          Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.

          We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 x 10(-7)), near MAF (encoding the transcription factor c-MAF, P = 3.8 x 10(-13)) and near PTER (phosphotriesterase-related gene, P = 2.1 x 10(-7)).
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            Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin.

            Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism. This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry. Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site. The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.
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              Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.

              Obesity is more linked to vascular disease, including atherosclerosis and restenotic change, after balloon angioplasty. The precise mechanism linking obesity and vascular disease is still unclear. Previously we have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, decreases in obese subjects, and that hypoadiponectinemia is associated to ischemic heart disease. In current the study, we investigated the in vivo role of adiponectin on the neointimal thickening after artery injury using adiponectin-deficient mice and adiponectin-producing adenovirus. Adiponectin-deficient mice showed severe neointimal thickening and increased proliferation of vascular smooth muscle cells in mechanically injured arteries. Adenovirus-mediated supplement of adiponectin attenuated neointimal proliferation. In cultured smooth muscle cells, adiponectin attenuated DNA synthesis induced by growth factors including platelet-derived growth factor, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), basic fibroblast growth factor, and EGF and cell proliferation and migration induced by HB-EGF. In cultured endothelial cells, adiponectin attenuated HB-EGF expression stimulated by tumor necrosis factor alpha. The current study suggests an adipo-vascular axis, a direct link between fat and artery. A therapeutic strategy to increase plasma adiponectin should be useful in preventing vascular restenosis after angioplasty.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                nh
                Nutrición Hospitalaria
                Nutr. Hosp.
                Grupo Arán (Madrid, Madrid, Spain )
                0212-1611
                1699-5198
                August 2012
                : 27
                : 4
                : 1184-1189
                Affiliations
                [01] Valladolid orgnameUniversidad de Valladolid orgdiv1Hospital Río Ortega orgdiv2Facultad de Medicina España
                Article
                S0212-16112012000400032
                10.3305/nh.2012.27.4.5851
                23165561
                615ffed9-4349-43df-a339-43dea61d1447

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 21 April 2012
                : 13 March 2012
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 35, Pages: 6
                Product

                SciELO Spain


                Adipocitoquinas,Factores de riesgo cardiovascular,rs9939609,Obesidad mórbida,Adipokines,Cardiovascular risk factors,Morbid obesity

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