title: Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation.
abstract: 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.
authors.affiliation: Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ramírez
authors.forename: Patricia
authors.initials: P
authors.lastname: Andrada
authors.forename: Fernando
authors.initials: F
authors.lastname: Rotellar
authors.forename: Víctor
authors.initials: V
authors.lastname: Valentí
authors.forename: Rafael
authors.initials: R
authors.lastname: Moncada
authors.forename: Pablo
authors.initials: P
authors.lastname: Martí
authors.forename: Camilo
authors.initials: C
authors.lastname: Silva
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
chemical_list: D007328:Insulin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1