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

Abstract

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.

Pituitary adenylate cyclase-activating polypeptide ameliorates vascular dysfunction induced by hyperglycaemia

“…34 NOV is an adipocytokine involved in obesity-associated insulin resistance. According to a recent study 37 NOV−/− mice on high fat diet had lower body weight, lower fat mass and improved glucose tolerance and insulin sensitivity. Our data show that FGF basic, MMP-9 and NOV are sensitive vascular markers and are able to indicate already a shortterm hyperglycaemia.…”

The association of NOV/CCN3 with obstructive sleep apnea (OSA): preliminary evidence of a novel biomarker in OSA

“…In a mouse model of inflammatory renal disease, NOV-/-mice had lower levels of CCL2, VCAM-1, IL-6 and CD68 mRNA compared with wild type mice [14]. Finally, NOV was shown to have significant metabolic effects in an animal model: NOV-/-mice fed a high fat diet (HFD) compared with wild type mice fed HFD demonstrated lower weight, lower fat mass, higher proportion of small adipocytes, higher energy expenditure gene expression, improved glucose tolerance and energy expenditure, and a shift towards a less pro-inflammatory phenotype [16]. Higher NOV levels/induction of NOV results in increased adipose tissue deposition and enhanced cholesterol and plasma triglyceride formation in human cardio-metabolic patients [15].…”

“…A recent study demonstrated that NOV is independently associated with body mass index (BMI) and fat mass, decreases with weight loss, and is present in adipose tissue in both humans and mice [15]. In a follow-up study, the same group demonstrated in NOV knockout mice that NOV-/-mice fed a high-fat diet had decreased weight and fat mass, improved glucose tolerance/insulin sensitivity and a marked decrease in the expression of pro-inflammatory cytokines from adipose tissue [16].…”

Adipocyte Glucocorticoid Receptor Deficiency Promotes Adipose Tissue Expandability and Improves the Metabolic Profile Under Corticosterone Exposure

“…Macrophages were isolated from SCAT and GAT from WT and AdipoGR-KO mice treated with CORT and stained as described previously (27). Stained cells were analyzed using a Gallios flow cytometer (Beckman Coulter, Villepinte, France), and data were processed using Kaluza software (Beckman Coulter).…”