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Nutrients 2015, 7(6), 4465-4479; doi:10.3390/nu7064465

NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients

1
Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524—Cidade Universitária, Sao Paulo, 05508-000, Brazil
2
Department of Clinical Surgery, University of Sao Paulo, Av. Prof. Lineu Prestes, 2565—Cidade Universitária, São Paulo, 05508-000, Brazil
3
Biotechnology Group, Laboratory of Adipose Tissue Biology, University of Mogi das Cruzes, Mogi das Cruzes, Sao Paulo, 05508-100, Brazil
4
Department of Nutritional Biochemistry, University of Potsdam, Potsdam, 14558, Germany,
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Received: 9 April 2015 / Revised: 25 May 2015 / Accepted: 25 May 2015 / Published: 4 June 2015
(This article belongs to the Special Issue Nutrition and Cancer)
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Abstract

Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1β, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1β, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia. View Full-Text
Keywords: cancer cachexia; inflammation; white adipose tissue; NF-κB; IκB cancer cachexia; inflammation; white adipose tissue; NF-κB; IκB
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. (CC BY 4.0).

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MDPI and ACS Style

Camargo, R.G.; Riccardi, D.M.R.; Ribeiro, H.Q.T.; Carnevali, L.C., Jr.; de Matos-Neto, E.M.; Enjiu, L.; Neves, R.X.; Lima, J.D.C.C.; Figuerêdo, R.G.; de Alcântara, P.S.M.; Maximiano, L.; Otoch, J.; Batista, M.L., Jr.; Püschel, G.; Seelaender, M. NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients. Nutrients 2015, 7, 4465-4479.

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