title: Adipocyte CREB promotes insulin resistance in obesity.
abstract: Increases in adiposity trigger metabolic and inflammatory changes that interfere with insulin action in peripheral tissues, culminating in beta cell failure and overt diabetes. We found that the cAMP Response Element Binding protein (CREB) is activated in adipose cells under obese conditions, where it promotes insulin resistance by triggering expression of the transcriptional repressor ATF3 and thereby downregulating expression of the adipokine hormone adiponectin as well as the insulin-sensitive glucose transporter 4 (GLUT4). Transgenic mice expressing a dominant-negative CREB transgene in adipocytes displayed increased whole-body insulin sensitivity in the contexts of diet-induced and genetic obesity, and they were protected from the development of hepatic steatosis and adipose tissue inflammation. These results indicate that adipocyte CREB provides an early signal in the progression to type 2 diabetes.
authors.affiliation: Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
authors.forename: Maziyar
authors.initials: M
authors.lastname: Saberi
authors.forename: Erik
authors.initials: E
authors.lastname: Zmuda
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Wang
authors.forename: Judith
authors.initials: J
authors.lastname: Altarejos
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhang
authors.forename: Renaud
authors.initials: R
authors.lastname: Dentin
authors.forename: Susie
authors.initials: S
authors.lastname: Hedrick
authors.forename: Gautam
authors.initials: G
authors.lastname: Bandyopadhyay
authors.forename: Tsonwin
authors.initials: T
authors.lastname: Hai
authors.forename: Jerry
authors.initials: J
authors.lastname: Olefsky
authors.forename: Marc
authors.initials: M
authors.lastname: Montminy
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005943:Gluconeogenesis / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; D052242:Adiponectin; C103002:Atf3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D014157:Transcription Factors; D000263:Adenylate Kinase