title: Expression of Caveolin 1 is enhanced by DNA demethylation during adipocyte differentiation. status of insulin signaling.
abstract: Caveolin 1 (Cav-1) is an essential constituent of adipocyte caveolae which binds the beta subunit of the insulin receptor (IR) and is implicated in the regulation of insulin signaling. We have found that, during adipocyte differentiation of 3T3-L1 cells the promoter, exon 1 and first intron of the Cav-1 gene undergo a demethylation process that is accompanied by a strong induction of Cav-1 expression, indicating that epigenetic mechanisms must have a pivotal role in this differentiation process. Furthermore, IR, PKB-Akt and Glut-4 expression are also increased during the differentiation process suggesting a coordinated regulation with Cav-1. Activation of Cav-1 protein by phosphorylation arises during the differentiation process, yet in fully mature adipocytes insulin is no longer able to significantly increase Cav-1 phosphorylation. However, these long-term differentiated cells are still able to respond adequately to insulin, increasing IR and PKB-Akt phosphorylation and glucose uptake. The activation of Cav-1 during the adipocyte differentiation process could facilitate the maintenance of insulin sensitivity by these fully mature adipocytes isolated from additional external stimuli. However, under the influence of physiological conditions associated to obesity, such as chronic inflammation and hypoxia, insulin sensitivity would finally be compromised.
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Palacios-Ortega
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Varela-Guruceaga
authors.affiliation: Department of Nutrition Food Science and Physiology, University of Navarra, Pamplona, Spain; Physiopathology of Obesity and Nutrition CIBERobn, Carlos III Health Research Institute, Madrid, Spain.
authors.forename: Fermín Ignacio
authors.initials: FI
authors.lastname: Milagro
authors.affiliation: Department of Nutrition Food Science and Physiology, University of Navarra, Pamplona, Spain; Physiopathology of Obesity and Nutrition CIBERobn, Carlos III Health Research Institute, Madrid, Spain.
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain; Physiopathology of Obesity and Nutrition CIBERobn, Carlos III Health Research Institute, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de Miguel
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003847:Deoxyglucose / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007438:Introns / Q000235:genetics; D020738:Leptin / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D052242:Adiponectin; D051242:Caveolin 1; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D003847:Deoxyglucose
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