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

• DOI: 10.2337/db15-0617
• Publication Date: 2016-06-10T02:30:15Z
• Authors: Cécile Martinerie; Marie Garcia; Thi Thu Huong Do; Bénédicte Antoine; Marthe Moldes; Guillaume Dorothee; Chantal Kazazian; Martine Auclair; Marion Buyse; Tatiana Ledent; Pierre-Olivier Ma...; Maria Fesatidou; Adrien Beisseiche; Haruhiko Koseki; Shuichi Hiraoka; Christos Evangelo...; Bertrand Blondeau; Raphael Georges D...; Serge Luquet; Bruno Fève
• Keywords: Proinflammatory cytokine; Energy homeostasis; Adipose tissue macrophages

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