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Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation

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The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling pathway that has been proposed as a key molecular factor in insulin resistance development under conditions of nutrient overload. The aim was to evaluate the involvement of S6K1 in obesity as well as to explore their association with visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects were used. Gene expression levels of RPS6KB1 and key inflammatory markers were analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were increased (P < 0.05) in obese patients. Insulin treatment significantly enhanced (P < 0.01) gene expression levels of RPS6KB1 and a positive association (P < 0.05) of RPS6KB1 expression with different markers of insulin resistance was observed. Moreover, RPS6KB1 gene expression levels were positively correlated with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2, MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8, representative players involved in signalling pathways related to S6K1. The increased levels of S6K1 in obesity and its positive association with insulin resistance and inflammation suggest a role for this protein in the changes that take place in VAT in obesity establishing a link between inflammation and a higher risk for the development of metabolic diseases.

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Acknowledgments

This work was supported by Fondo de Investigación Sanitaria-FEDER (PI11/02681, PI12/00515 and PI13/00460) from the Spanish Instituto de Salud Carlos III and by the Department of Health (48/2011 and 58/2011) of the Gobierno de Navarra of Spain. The authors gratefully acknowledge the valuable collaboration of all the members of the Multidisciplinary Obesity Team, Clínica Universidad de Navarra, Pamplona, Spain. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Spain.

Conflict of interest

Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Patricia Andrada, Fernando Rotellar, Víctor Valentí, Rafael Moncada, Pablo Martí, Camilo Silva, Javier Salvador, Gema Frühbeck declare that they have no conflict of interest.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain

    Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez & Gema Frühbeck

  2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Pamplona, Spain

    Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Fernando Rotellar, Víctor Valentí, Camilo Silva, Javier Salvador & Gema Frühbeck

  3. Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Avda. Pío XII, 36, 31008, Pamplona, Spain

    Patricia Andrada, Camilo Silva, Javier Salvador & Gema Frühbeck

  4. Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain

    Fernando Rotellar, Víctor Valentí & Pablo Martí

  5. Department of Anesthesia, Clínica Universidad de Navarra, Pamplona, Spain

    Rafael Moncada

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  1. Victoria Catalán
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Correspondence to Gema Frühbeck.

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Catalán, V., Gómez-Ambrosi, J., Rodríguez, A. et al. Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation. Acta Diabetol 52, 257–266 (2015). https://doi.org/10.1007/s00592-014-0632-9

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