title: NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients.
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.
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. rodolfogcamargo@usp.br.
authors.forename: Rodolfo Gonzalez
authors.initials: RG
authors.lastname: Camargo
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. dariccardi@hotmail.com.
authors.forename: Daniela Mendes Dos Reis
authors.initials: DM
authors.lastname: Riccardi
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. henriqueribeiro@hotmail.com.
authors.forename: Henrique Quintas Teixeira
authors.initials: HQ
authors.lastname: Ribeiro
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. lucarjr78@hotmail.com.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Carnevali
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. emidiomatos@gmail.com.
authors.forename: Emidio Marques
authors.initials: EM
authors.lastname: de Matos-Neto
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. enjiu84@gmail.com.
authors.forename: Lucas
authors.initials: L
authors.lastname: Enjiu
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. digo_e.d@hotmail.com.
authors.forename: Rodrigo Xavier
authors.initials: RX
authors.lastname: Neves
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. joana.carola14@gmail.com.
authors.forename: Joanna Darck Carola Correia
authors.initials: JD
authors.lastname: Lima
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. raquel.galfig@gmail.com.
authors.forename: Raquel Galvão
authors.initials: RG
authors.lastname: Figuerêdo
authors.affiliation: Department of Clinical Surgery, University of Sao Paulo, Av. Prof. Lineu Prestes, 2565-Cidade Universitária, São Paulo, 05508-000, Brazil. palcantara@usp.br.
authors.forename: Paulo Sérgio Martins
authors.initials: PS
authors.lastname: de Alcântara
authors.affiliation: Department of Clinical Surgery, University of Sao Paulo, Av. Prof. Lineu Prestes, 2565-Cidade Universitária, São Paulo, 05508-000, Brazil. linda@usp.br.
authors.forename: Linda
authors.initials: L
authors.lastname: Maximiano
authors.affiliation: Department of Clinical Surgery, University of Sao Paulo, Av. Prof. Lineu Prestes, 2565-Cidade Universitária, São Paulo, 05508-000, Brazil. pinhata@usp.br.
authors.forename: José
authors.initials: J
authors.lastname: Otoch
authors.affiliation: Biotechnology Group, Laboratory of Adipose Tissue Biology, University of Mogi das Cruzes, Mogi das Cruzes, Sao Paulo, 05508-100, Brazil. migueljr4@me.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Batista
authors.affiliation: Department of Nutritional Biochemistry, University of Potsdam, Potsdam, 14558, Germany,. gpuesche@uni-potsdam.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Püschel
authors.affiliation: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524-Cidade Universitária, Sao Paulo, 05508-000, Brazil. seelaend@icb.usp.br.
authors.forename: Marilia
authors.initials: M
authors.lastname: Seelaender
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002100:Cachexia / Q000473:pathology*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D009369:Neoplasms / Q000473:pathology*; D011788:Quality of Life; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; C573415:IFNG protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D007371:Interferon-gamma
keywords: IκB; NF-κB; cancer cachexia; inflammation; white adipose tissue