NOV/CCN3: A New Adipocytokine Involved in Obesity-Associated Insulin Resistance.
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.
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Cécile
C
Martinerie
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Marie
M
Garcia
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Thi Thu Huong
TT
Do
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Bénédicte
B
Antoine
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Marthe
M
Moldes
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France.
Guillaume
G
Dorothee
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Chantal
C
Kazazian
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Martine
M
Auclair
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France Department of Pharmacy, Assistance Publique-Hôpitaux de Paris, Saint-Antoine Hospital, Paris, France Paris-Sud University, EA 4123, Châtenay-Malabry, France.
Marion
M
Buyse
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France.
Tatiana
T
Ledent
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Pierre-Olivier
PO
Marchal
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France.
Maria
M
Fesatidou
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Cordeliers Research Center, Paris, France.
Adrien
A
Beisseiche
RIKEN Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama, Japan.
Haruhiko
H
Koseki
Department of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
Shuichi
S
Hiraoka
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Tenon Hospital, Paris, France.
Christos Evangelos
CE
Chadjichristos
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Cordeliers Research Center, Paris, France.
Bertrand
B
Blondeau
Sorbonne Paris City University, Paris Diderot University, BFA, CNRS, Paris, France.
Raphael Georges
RG
Denis
Sorbonne Paris City University, Paris Diderot University, BFA, CNRS, Paris, France.
Serge
S
Luquet
Sorbonne Universities, Pierre and Marie Curie University Paris 06, INSERM, Saint-Antoine Research Center, Saint-Antoine Hospital, Paris, France Hospitalo-Universitary Institute, ICAN, Paris, France Department of Endocrinology, Paris, Assistance Publique-Hôpitaux de Paris, Saint-Antoine Hospital, Paris, France bfeve@free.fr.
Bruno
B
Fève
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055514:Nephroblastoma Overexpressed Protein / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010179:Pancreas / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
C526320:Ccn3 protein, mouse; D055514:Nephroblastoma Overexpressed Protein; D034741:RNA, Small Interfering