title: Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation.
abstract: To investigate the role of DRO1 in obesity and adipogenesis in vivo, we generated a constitutive Dro1 knockout mouse model and analyzed the effect of DRO1 loss on body growth under standard and high fat diet feeding conditions. Loss of DRO1 resulted in a significant increase in body weight which was accompanied by a substantial expansion of white adipose tissue depots. The obese phenotype could be further enhanced by a high fat dietary challenge which also resulted in impaired glucose metabolism and the development of hepatosteatosis in Dro1 knockout mice. To study the role of DRO1 in adipocyte differentiation, primary stromal-vascular (SV) cells were isolated from inguinal white fat pads of knockout and control mice. In primary SV cells, depletion of DRO1 significantly promoted adipogenesis with upregulation of markers for adipogenesis (Cebpa, Pparg, Adipoq) and lipid metabolism (Dgat1, Dgat2). Our results demonstrate that DRO1 is a crucial regulator of energy homeostasis in vivo and functions as an inhibitor of adipogenesis in primary cells.
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany. Electronic address: grill@genzentrum.lmu.de.
authors.forename: Jessica I
authors.initials: JI
authors.lastname: Grill
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herbst
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ofner
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hiltwein
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany.
authors.forename: Maximilian K
authors.initials: MK
authors.lastname: Marschall
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Zierahn
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, Munich, Germany.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Schneider
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Internal Medicine and Gastroenterology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Kolligs
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D050156:Adipogenesis; D000273:Adipose Tissue; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002454:Cell Differentiation; D059305:Diet, High-Fat; D016326:Extracellular Matrix Proteins; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005247:Feeding Behavior; D005260:Female; D005947:Glucose / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D017154:Stromal Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C448780:Ccdc80 protein, mouse; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D005947:Glucose
keywords: Adipogenesis; CCDC80; DRO1; Obesity