Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Pakradouni, Jihane; Goff, Wilfried Le; Calmel, Claire; Antoine, B; Villard, Elise F.; Frisdal, Éric; Abifadel, Marianne; Tordjman, Joan; Poitou, Christine; Bonnefont‐Rousselot, Dominique; Bittar, Randa; Bruckert, Éric; Clément, Karine; Fève, Bruno; Martinerie, Cécile; Guérin, Maryse

doi:10.1371/journal.pone.0066788

Cited by 43 publications

(58 citation statements)

References 39 publications

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“…Thus, the weight loss-induced changes in circulating WISP1 most likely originated from adipose tissue rather than from the liver or other organs. Another CCN family member, NOV, also is associated with obesity, and NOV levels in circulation are decreased after weight reduction due to bariatric surgery (11). In line with the present data, circulating NOV levels are higher in women than in men (11).…”

Section: Discussionsupporting

confidence: 89%

“…Another CCN family member, NOV, also is associated with obesity, and NOV levels in circulation are decreased after weight reduction due to bariatric surgery (11). In line with the present data, circulating NOV levels are higher in women than in men (11). Thus, the sex differences in the changes of WISP1 concentration after weight loss in the present study might reflect regulation of CCN peptide production by sex hormones (28) and needs further investigation.…”

Section: Discussionsupporting

confidence: 83%

“…Studies have shown that other CCN family members are closely linked to adipogenesis (5,6,11), but no data exist about the role of WISP1/CCN4 in obesity and associated diseases. We found that WISP1 gene expression and WISP1 protein production is upregulated during human adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental evidence suggests that other CCN family members, such as WISP2 and nephroblastoma overexpressed protein (NOV), participate in the pathogenesis of obesity and associated diseases (5,6,11,12), but no data are available on the possible relationship between WISP1 and obesity. Similar to the majority of CCN proteins, WISP1 consists of four globular modules analogous to various extracellular protein domains.…”

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confidence: 99%

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WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

et al. 2014

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WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix–associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

et al. 2014

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“…Measurements of plasma NOV concentrations in a large cohort of patients screened for cardiometabolic diseases, in which 60% of the patients had a BMI above 30 kg/m 2 , revealed, for the first time, a strong relationship between plasma NOV concentrations and obesity (21). Plasma NOV levels were also correlated with weight loss in patients who had undergone bariatric surgery.…”

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confidence: 92%

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

et al. 2016

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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.

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Cardioprotective Heme Oxygenase‐1‐PGC1α Signaling in Epicardial Fat Attenuates Cardiovascular Risk in Humans as in Obese Mice

Singh

McClung

Thompson

et al. 2019

Obesity

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Objective This study investigated whether levels of signaling pathways and inflammatory adipokines in epicardial fat regulate cardiovascular risks in humans and mice. Methods Epicardial fat was obtained from the hearts of patients with heart failure requiring coronary artery bypass surgery, and signaling pathways were compared with visceral fat. The genetic profile of epicardial and visceral fat from humans was also compared with genetic profiles of epicardial and visceral fat in obese mice. Left ventricular (LV) fractional shortening was measured in obese mice before and after treatment with inducers of mitochondrial signaling heme oxygenase 1 (HO‐1)‐peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α). An RNA array/heat map on 88 genes that regulate adipose tissue function was used to identify a target gene network. Results Human epicardial fat gene profiling showed decreased levels of mitochondrial signaling of HO‐1‐PGC1α and increased levels of the inflammatory adipokine CCN family member 3. Similar observations were seen in epicardial and visceral fat of obese mice. Improvement in LV function was linked to the increase in mitochondrial signaling in epicardial fat of obese mice. Conclusions There is a link between cardiac ectopic fat deposition and cardiac function in humans that is similar to that which is described in obese mice. An increase of mitochondrial signaling pathway gene expression in epicardial fat attenuates cardiometabolic dysfunction and LV fractional shortening in obese mice.

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Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Cited by 43 publications

References 39 publications

WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

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

Cardioprotective Heme Oxygenase‐1‐PGC1α Signaling in Epicardial Fat Attenuates Cardiovascular Risk in Humans as in Obese Mice

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