title: Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression.
abstract: OBJECTIVE
  The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans.
  
  
  METHODS
  p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated.
  
  
  RESULTS
  Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes.
  
  
  CONCLUSIONS
  Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital "Dr Josep Trueta" of Girona, Girona, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Ortega
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital "Dr Josep Trueta" of Girona, Girona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Endocrinology and Nutrition, Hospital Clínico Universitario Virgen de Victoria de Málaga, Málaga, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Mayas
authors.affiliation: INSERM Unité 858, Institut de Médecine Moléculaire de Rangueil, Université Paul Sabatier, IFR31, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Serino
authors.affiliation: Department of Surgery, Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Rodriguez-Hermosa
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital "Dr Josep Trueta" of Girona, Girona, Spain.
authors.forename: W
authors.initials: W
authors.lastname: Ricart
authors.affiliation: INSERM Unité 858, Institut de Médecine Moléculaire de Rangueil, Université Paul Sabatier, IFR31, Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Luche
authors.affiliation: INSERM Unité 858, Institut de Médecine Moléculaire de Rangueil, Université Paul Sabatier, IFR31, Toulouse, France.
authors.forename: R
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Endocrinology and Nutrition, Hospital Clínico Universitario Virgen de Victoria de Málaga, Málaga, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Department of Endocrinology & Nutrition, Clínica Universidad de Navarra-CIBERobn CBO6/03/1014, Pamplona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Frühbeck
authors.affiliation: Institute of Internal Medicine, Catholic University of Rome, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mingrone
authors.affiliation: 1] CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/0010), and Instituto de Salud Carlos III (ISCIII), Santiago de Compostela, Spain [2] Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital "Dr Josep Trueta" of Girona, Girona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D050110:Bariatric Surgery; D059305:Diet, High-Fat; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D009852:Omentum / Q000378:metabolism* / Q000601:surgery; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin