Connective tissue growth factor/CCN-2 is upregulated in epididymal and subcutaneous fat depots in a dietary-induced obesity model

• Published in: American journal of physiology: endocrinology and metabolism 2013-06, Vol.304 (12), p.E1291-E1302
• Main Authors: Tan, Joanne T M, McLennan, Susan V, Williams, Paul F, Rezaeizadeh, Alireza, Lo, Lisa W-Y, Bonner, James G, Twigg, Stephen M
• Format: Article
• Language: English
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis - physiology; Animals; Body fat; Cell Differentiation - physiology; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diet; Dietary Fats - pharmacology; Disease Models, Animal; Epididymis - metabolism; Genes; Insulin Resistance - physiology; Male; Mice; Mice, Inbred C57BL; Obesity; Obesity - metabolism; Pathogenesis; RNA, Messenger - metabolism; Subcutaneous Fat, Abdominal - metabolism; Tissues; Up-Regulation - physiology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00654.2012

Connective tissue growth factor (CTGF), also known as CCN-2, is a cysteine-rich secreted protein that is involved in a range of biological processes, including regulation of cell growth and differentiation. Our previous in vitro studies have shown that CCN-2 inhibits adipocyte differentiation, although whether CCN-2 is regulated in vivo in adipogenesis is undetermined and was investigated in this study. C57BL/6 male mice were fed either standard laboratory chow (ND) or a diet high in fat (HFD; 45% fat) for 15 or 24 wk. HFD animals that gained >5 g in weight (termed HFD-fat) were insulin resistant and were compared with HFD-fed animals, which failed to gain weight (termed HFD-lean). HFD-fat mice had significantly increased CCN-2 mRNA levels in both the subcutaneous and epididymal fat pads, whereas CCN-2 mRNA was not induced in the epididymal site in HFD-lean mice. Also in HFD-fed animals, epididymal CCN-2 mRNA correlated positively with key genes involved in adipocyte differentiation, adiponectin and PPARγ (P < 0.001 and P < 0.002, respectively). Additionally, epididymal CCN-2 mRNA correlated positively with two markers of tissue turnover, PAI-1 in HFD-fat mice only and TIMP-1, but only in the HFD-lean mice. Collectively, these findings suggest that CCN-2 plays a role in adipocyte differentiation in vivo and thus in the pathogenesis of obesity linked with insulin resistance.