title: Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix.
abstract: The role of the extracellular matrix (ECM) in regulating adipocyte metabolism in the context of metabolic disease is poorly defined.
  
  
  
  The objective of this study was to define the metabolic phenotype of adipocytes associated with human diabetes (DM) and the role of the ECM in regulating adipocyte metabolism.
  
  
  
  Adipose tissues from obese patients were studied in standard 2-dimensional (2D) cell culture and an in vitro model of decellularized adipose tissue ECM repopulated with human adipocytes, and results were correlated with DM status.
  
  
  
  This study was conducted at the Academic University Medical Center and Veteran's Administration Hospital.
  
  
  
  Seventy patients with morbid obesity undergoing bariatric surgery were included in the study.
  
  
  
  Visceral and subcutaneous adipose tissues were collected at the time of bariatric surgery.
  
  
  
  This study used metabolic assays for glucose uptake, lipolysis, and lipogenesis in adipocytes in 2D cell culture and 3-dimensional ECM culture.
  
  
  
  Adipocytes from subjects with DM manifest decreased glucose uptake and decreased lipolysis in 2D culture. ECM supports differentiation of mature adipocytes and recapitulates DM-specific differences in adipocyte metabolism observed in 2D culture. ECM from subjects without DM partially rescues glucose uptake and lipolytic defects in adipocytes from subjects with DM, whereas ECM from subjects with DM impairs glucose uptake in adipocytes from subjects without DM.
  
  
  
  DM is associated with adipocyte metabolic dysfunction. The ECM regulates adipocyte metabolism. Nondiabetic ECM rescues metabolic dysfunction in DM adipocytes, whereas DM ECM imparts features of metabolic dysfunction to nondiabetic adipocytes. These findings suggest the ECM as a target for manipulating adipose tissue metabolism.
authors.affiliation: Department of Surgery.
authors.forename: Nicki A
authors.initials: NA
authors.lastname: Baker
authors.affiliation: Department of Pediatrics and Communicable Diseases.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Muir
authors.affiliation: Department of Surgery.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Washabaugh
authors.affiliation: Department of Surgery.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Neeley
authors.affiliation: Center for Statistical Consultation & Research and.
authors.forename: Sophie Yu-Pu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Undergraduate Research Opportunity Program, University of Michigan, Ann Arbor, Michigan 48109; and.
authors.forename: Carmen G
authors.initials: CG
authors.lastname: Flesher
authors.affiliation: Undergraduate Research Opportunity Program, University of Michigan, Ann Arbor, Michigan 48109; and.
authors.forename: John
authors.initials: J
authors.lastname: Vorwald
authors.affiliation: Department of Surgery.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Finks
authors.affiliation: Department of Surgery.|Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, Michigan 48109.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Ghaferi
authors.affiliation: Department of Surgery.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mulholland
authors.affiliation: Department of Surgery.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Varban
authors.affiliation: Department of Pediatrics and Communicable Diseases.|Graduate Program in Immunology, and.|Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Carey N
authors.initials: CN
authors.lastname: Lumeng
authors.affiliation: Department of Surgery.|Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, Michigan 48109.
authors.forename: Robert W
authors.initials: RW
authors.lastname: O'Rourke
mesh_terms: D050153:Abdominal Fat / Q000166:cytology / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D000328:Adult; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000378:metabolism; D050155:Lipogenesis; D008066:Lipolysis; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005947:Glucose