Plasma NOV/CCN3 levels are closely associated with obesity in patients with metabolic disorders

PLoS One. 2013 Jun 13;8(6):e66788. doi: 10.1371/journal.pone.0066788. Print 2013.


Objective: Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans.

Methods: NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m(2). Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages.

Results: After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet.

Conclusion: Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adult
  • Aged
  • Animals
  • Blood Glucose
  • Body Composition
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Diet, High-Fat
  • Female
  • Humans
  • Lipid Metabolism
  • Male
  • Metabolic Diseases / blood*
  • Metabolic Diseases / complications*
  • Metabolic Diseases / metabolism
  • Mice
  • Middle Aged
  • Nephroblastoma Overexpressed Protein / blood*
  • Nephroblastoma Overexpressed Protein / metabolism
  • Obesity / blood*
  • Obesity / complications*
  • Obesity / metabolism
  • Risk Factors


  • Blood Glucose
  • CCN3 protein, human
  • Nephroblastoma Overexpressed Protein
  • C-Reactive Protein

Grants and funding

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), and by grants from the Institut National du Cancer (INCA) and the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC). JP was a recipient of financial support from the ANRT (Association National Recherche et Technologie), CIFRE. The authors acknowledge support from the Assistance Publique-Hôpitaux de Paris (APHP) and the Direction of Clinical Research (CRC), which promoted and supported our clinical investigation (CRC NCT 0047658) and PHRC 0702. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.