title: Connective tissue growth factor/CCN-2 is upregulated in epididymal and subcutaneous fat depots in a dietary-induced obesity model.
abstract: 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.
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; and.
authors.forename: Joanne T M
authors.initials: JT
authors.lastname: Tan
authors.forename: Susan V
authors.initials: SV
authors.lastname: McLennan
authors.forename: Paul F
authors.initials: PF
authors.lastname: Williams
authors.forename: Alireza
authors.initials: A
authors.lastname: Rezaeizadeh
authors.forename: Lisa W-Y
authors.initials: LW
authors.lastname: Lo
authors.forename: James G
authors.initials: JG
authors.lastname: Bonner
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D004822:Epididymis / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C526316:CCN2 protein, rat; D004041:Dietary Fats; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor
keywords: adipose tissue; connective tissue growth factor; fat cell differentiation; insulin resistance