Soledad López1,2,3, Sara García-Serrano4,5, Carolina Gutierrez-Repiso6, Francisca Rodríguez-Pacheco4, Ailec Ho-Plagaro7, Concepción Santiago-Fernandez7, Gonzalo Alba8, Marta Cejudo-Guillen9, Alberto Rodríguez-Cañete10, Sergio Valdes5,6, Lourdes Garrido-Sanchez4,11, David Pozo8,9, Eduardo García-Fuentes12,13,14. 1. Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, Seville, Spain. slopez9@us.es. 2. CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine (CSIC-University of Seville-UPO-Junta de Andalucia), Seville, Spain. slopez9@us.es. 3. Dpto. Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain. slopez9@us.es. 4. Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Malaga, Spain. 5. CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos III, Malaga, Spain. 6. Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Malaga, Spain. 7. Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Malaga, Spain. 8. Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, Seville, Spain. 9. CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine (CSIC-University of Seville-UPO-Junta de Andalucia), Seville, Spain. 10. Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario, Malaga, Spain. 11. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Malaga, Spain. 12. Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Malaga, Spain. edugf1@gmail.com. 13. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Malaga, Spain. edugf1@gmail.com. 14. Laboratorio de Investigación, Hospital Civil, Plaza del Hospital Civil s/n, 29009, Malaga, Spain. edugf1@gmail.com.
Abstract
BACKGROUND: The immune response of visceral adipose tissue (VAT) in obesity, in particular the role of invariant natural killer T (iNKT) cells, has not yet been fully elucidated. OBJECTIVE: To characterize iNKT cells and its activation status in VAT and peripheral blood mononuclear cells (PBMC) in morbidly obese subjects (MO), and to analyze their association with metabolic parameters. SUBJECTS AND METHODS: Twenty non-obese and 20 MO subjects underwent Roux-en-Y gastric bypass (RYGB) and were studied before and 6 months after RYGB. VAT and PBMC were obtained. RESULTS: A decrease in VAT iNKT cells from MO was found, however, not in PBMC. Visceral adipocytes from MO presented increased CD1d expression (p = 0.032). MO presented an increase in early activated CD69+ iNKT cells in PBMC before RYGB (p < 0.001), but not after RYGB nor in VAT, and an increase in later activated CD25+ iNKT in VAT (p = 0.046), without differences in PBMC. The co-expression of early and later markers (CD69+CD25+) in iNKT cells was increased in MO in VAT (p = 0.050) and PBMC (p = 0.006), decreasing after RYGB (p = 0.050). CD69+ iNKT and CD69+CD25+ iNKT cells in PBMC after RYGB correlated negatively with glucose, insulin, and insulin resistance levels. CONCLUSIONS: There is a tissue-specific phenotype and activation of iNKT cells in VAT in morbid obesity, which could be involved in VAT immunometabolism dysregulation. Also, the increase in CD1d expression could be to offset the lack of VAT iNKT cells.
BACKGROUND: The immune response of visceral adipose tissue (VAT) in obesity, in particular the role of invariant natural killer T (iNKT) cells, has not yet been fully elucidated. OBJECTIVE: To characterize iNKT cells and its activation status in VAT and peripheral blood mononuclear cells (PBMC) in morbidly obese subjects (MO), and to analyze their association with metabolic parameters. SUBJECTS AND METHODS: Twenty non-obese and 20 MO subjects underwent Roux-en-Y gastric bypass (RYGB) and were studied before and 6 months after RYGB. VAT and PBMC were obtained. RESULTS: A decrease in VAT iNKT cells from MO was found, however, not in PBMC. Visceral adipocytes from MO presented increased CD1d expression (p = 0.032). MO presented an increase in early activated CD69+ iNKT cells in PBMC before RYGB (p < 0.001), but not after RYGB nor in VAT, and an increase in later activated CD25+ iNKT in VAT (p = 0.046), without differences in PBMC. The co-expression of early and later markers (CD69+CD25+) in iNKT cells was increased in MO in VAT (p = 0.050) and PBMC (p = 0.006), decreasing after RYGB (p = 0.050). CD69+ iNKT and CD69+CD25+ iNKT cells in PBMC after RYGB correlated negatively with glucose, insulin, and insulin resistance levels. CONCLUSIONS: There is a tissue-specific phenotype and activation of iNKT cells in VAT in morbid obesity, which could be involved in VAT immunometabolism dysregulation. Also, the increase in CD1d expression could be to offset the lack of VAT iNKT cells.
Entities:
Keywords:
Adipose tissue; Inflammation; Natural killer T cells; Obesity
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