NOV/CCN3: A New Adipocytokine Involved in Obesity-Associated Insulin Resistance

Diabetes. 2016 Sep;65(9):2502-15. doi: 10.2337/db15-0617. Epub 2016 Jun 9.


Identification of new adipokines that potentially link obesity to insulin resistance represents a major challenge. We recently showed that NOV/CCN3, a multifunctional matricellular protein, is synthesized and secreted by adipose tissue, with plasma levels highly correlated with BMI. NOV involvement in tissue repair, fibrotic and inflammatory diseases, and cancer has been previously reported. However, its role in energy homeostasis remains unknown. We investigated the metabolic phenotype of NOV(-/-) mice fed a standard or high-fat diet (HFD). Strikingly, the weight of NOV(-/-) mice was markedly lower than that of wild-type mice but only on an HFD. This was related to a significant decrease in fat mass associated with an increased proportion of smaller adipocytes and to a higher expression of genes involved in energy expenditure. NOV(-/-) mice fed an HFD displayed improved glucose tolerance and insulin sensitivity. Interestingly, the absence of NOV was associated with a change in macrophages profile (M1-like to M2-like), in a marked decrease in adipose tissue expression of several proinflammatory cytokines and chemokines, and in enhanced insulin signaling. Conversely, NOV treatment of adipocytes increased chemokine expression. Altogether, these results show that NOV is a new adipocytokine that could be involved in obesity-associated insulin-resistance.

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism*
  • Adipose Tissue / physiopathology
  • Animals
  • Body Composition / genetics
  • Body Composition / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Diet, High-Fat / adverse effects
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Female
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / physiopathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • Liver / metabolism
  • Macrophages / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephroblastoma Overexpressed Protein / genetics
  • Nephroblastoma Overexpressed Protein / metabolism*
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Pancreas / metabolism
  • RNA, Small Interfering / genetics


  • Ccn3 protein, mouse
  • Nephroblastoma Overexpressed Protein
  • RNA, Small Interfering