PLoS ONE (Jan 2013)

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

  • Jihane Pakradouni,
  • Wilfried Le Goff,
  • Claire Calmel,
  • Bénédicte Antoine,
  • Elise Villard,
  • Eric Frisdal,
  • Marianne Abifadel,
  • Joan Tordjman,
  • Christine Poitou,
  • Dominique Bonnefont-Rousselot,
  • Randa Bittar,
  • Eric Bruckert,
  • Karine Clément,
  • Bruno Fève,
  • Cécile Martinerie,
  • Maryse Guérin

DOI
https://doi.org/10.1371/journal.pone.0066788
Journal volume & issue
Vol. 8, no. 6
p. e66788

Abstract

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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.