Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation

Mol Cell Endocrinol. 2017 Jan 5;439:286-296. doi: 10.1016/j.mce.2016.09.014. Epub 2016 Sep 16.


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.

Keywords: Adipogenesis; CCDC80; DRO1; Obesity.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adipogenesis
  • Adipose Tissue
  • Animals
  • Biomarkers / metabolism
  • Body Weight
  • Cell Differentiation*
  • Diet, High-Fat
  • Extracellular Matrix Proteins
  • Fatty Liver / complications
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Feeding Behavior
  • Female
  • Glucose / metabolism
  • Glycoproteins / deficiency*
  • Glycoproteins / metabolism
  • Intercellular Signaling Peptides and Proteins / deficiency*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice, Knockout
  • Obesity / complications
  • Obesity / metabolism*
  • Obesity / pathology*
  • Organ Size
  • Stromal Cells / metabolism
  • Up-Regulation


  • Biomarkers
  • Ccdc80 protein, mouse
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Glucose