A paradoxical but common finding in the obesity clinic is the identification of individuals who can be considered ‘inappropriately’ healthy for their degree of obesity. We think that studying these obese but metabolically healthy individuals and comparing them with equally obese but insulin-resistant individuals could provide important insights into the mechanistic link between adipose tissue expansion and associated metabolic alterations. In the present study, we investigated whether there are differences in inflammatory and insulin signalling pathways in VAT (visceral adipose tissue) that could account for the metabolic differences exhibited by morbidly obese individuals who are either insulin-resistant (IR-MO) or paradoxically insulin-sensitive (NIR-MO). Our results indicate that there are pathways common to obesity and unrelated to insulin resistance and others that are discriminative for insulin resistance for a similar degree of obesity. For instance, all morbidly obese patients, irrespective of their insulin resistance, showed increased expression of TNFα (tumour necrosis factor α) and activation of JNK1/2 (c-Jun N-terminal kinase 1/2). However, the IR-MO group showed significantly elevated expression levels of IL (interleukin)-1β and IL-6 and increased macrophage infiltrates compared with non-obese individuals and NIR-MO. IκBα [inhibitor of NF-κB (nuclear factor κB) α], the activation of ERK1/2 (extracellular-signal-regulated kinase 1/2) and NF-κB were discriminative of the state of insulin resistance and correlated with differential changes in IRS-1 (insulin receptor substrate 1) expression and Akt activation between IR-MO and NIR-MO individuals. Our results support the concept that NIR-MO individuals lack the inflammatory response that characterizes the IR-MO patient and that IL-6, IL-1β, ERK and NF-κB are important effectors that mediate the inflammation effects promoting insulin resistance.
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Research Article|
July 28 2010
The obese healthy paradox: is inflammation the answer?
Nuria Barbarroja;
Nuria Barbarroja
1
*Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria (Fundación IMABIS), Málaga, CIBER Fisiopatología de la Obesidad y Nutrición CB06/03, Instituto de Salud Carlos III, Spain
1To whom correspondence should be addressed (email nuria.barbarroja.exts@juntadeandalucia.es).
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Rosario López-Pedrera;
Rosario López-Pedrera
†Unidad de Investigación, Hospital Reina Sofía-IMIBIC, Córdoba, Spain
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Maria Dolores Mayas;
Maria Dolores Mayas
*Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria (Fundación IMABIS), Málaga, CIBER Fisiopatología de la Obesidad y Nutrición CB06/03, Instituto de Salud Carlos III, Spain
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Eduardo García-Fuentes;
Eduardo García-Fuentes
†Unidad de Investigación, Hospital Reina Sofía-IMIBIC, Córdoba, Spain
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Lourdes Garrido-Sánchez;
Lourdes Garrido-Sánchez
‡CIBERDEM, Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Spain
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M. Macías-González;
M. Macías-González
*Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria (Fundación IMABIS), Málaga, CIBER Fisiopatología de la Obesidad y Nutrición CB06/03, Instituto de Salud Carlos III, Spain
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Rajaa El Bekay;
Rajaa El Bekay
*Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria (Fundación IMABIS), Málaga, CIBER Fisiopatología de la Obesidad y Nutrición CB06/03, Instituto de Salud Carlos III, Spain
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Antonio Vidal-Puig;
Antonio Vidal-Puig
§Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, U.K.
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Francisco J. Tinahones
Francisco J. Tinahones
*Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria (Fundación IMABIS), Málaga, CIBER Fisiopatología de la Obesidad y Nutrición CB06/03, Instituto de Salud Carlos III, Spain
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Publisher: Portland Press Ltd
Received:
February 23 2010
Revision Received:
May 19 2010
Accepted:
June 03 2010
Accepted Manuscript online:
June 03 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 430 (1): 141–149.
Article history
Received:
February 23 2010
Revision Received:
May 19 2010
Accepted:
June 03 2010
Accepted Manuscript online:
June 03 2010
Connected Content
A commentary has been published:
Adipose tissue inflammation and insulin resistance: all obese humans are not created equal
Citation
Nuria Barbarroja, Rosario López-Pedrera, Maria Dolores Mayas, Eduardo García-Fuentes, Lourdes Garrido-Sánchez, M. Macías-González, Rajaa El Bekay, Antonio Vidal-Puig, Francisco J. Tinahones; The obese healthy paradox: is inflammation the answer?. Biochem J 15 August 2010; 430 (1): 141–149. doi: https://doi.org/10.1042/BJ20100285
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