Details

Autor(en) / Beteiligte

• Tan, Joanne T. M
• McLennan, Susan V
• Song, William W
• Lo, Lisa W.-Y
• Bonner, James G
• Williams, Paul F
• Twigg, Stephen M

Titel

Connective tissue growth factor inhibits adipocyte differentiation

Ist Teil von

• American Journal of Physiology: Cell Physiology, 2008-09, Vol.295 (3), p.C740-C751

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Discipline of Medicine, University of Sydney, Sydney; and 2 Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia Submitted 31 July 2007 ; accepted in final form 29 June 2008 Adipocyte differentiation is a key process implicated in the pathogenesis of obesity and insulin resistance. Its regulation is triggered by a cascade of transcription factors, including the CCAAT/enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated receptor- (PPAR ). Growth factors such as transforming growth factor-β1 (TGF-β1) are known to inhibit adipocyte differentiation in vitro, via the C/EBP pathway, and in vivo, but whether a downstream mediator of TGF-β1, connective tissue growth factor (CTGF), also known as CCN2, has a similar role is unknown. Mouse 3T3-L1 cells were differentiated into adipocytes by using standard methods, and effects and regulation of CTGF were studied. Intervention with recombinant human CTGF during differing stages of differentiation caused an inhibition in the development of the adipocyte phenotype, according to the gene expression of the differentiation markers adiponectin and PPAR , as well as suppression of lipid accumulation and expression of the lipogenic enzyme glycerol-3-phosphate dehydrogenase. Whereas CTGF gene expression promptly fell by 90% as 3T3-L1 preadipocytes differentiated into mature adipocytes, CTGF mRNA expression was induced by added TGF-β1. CTGF applied to cells early in the course of differentiation inhibited total cell protein levels and nuclear localization of the β-isoform of C/EBP (C/EBP-β) and, subsequently, total cell C/EBP- levels. CTGF also inhibited the adipocyte differentiation program in primary cultures of mouse preadipocytes. Expression of CTGF mRNA was twofold higher in the central fat depots of mice compared with subcutaneous fat, suggesting a potential role for CTGF in vivo. In summary, these data show that CTGF inhibits the adipocyte differentiation program. NIH/3T3; CCN2 Address for reprint requests and other correspondence: S. Twigg, Dept. of Endocrinology, Blackburn Bldg., DO6, and Discipline of Medicine, The Univ. of Sydney, NSW 2006, Australia (e-mail: stwigg{at}med.usyd.edu.au )