The CCN family of matricellular proteins directly or indirectly affects development and differentiation. A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740–C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations

A Leask

Andrew Leask

G Croissandeau

JTM Tan

M Fasshauer

MC Alessi

MD Lane

RA Ignotz

English

PubMed

Springer - Publisher Connector

The skinny on CCN2

Crossref

BITS AND BYTES
The skinny on CCN2
Andrew Leask
Received: 14 October 2008 /Accepted: 31 October 2008 /Published online: 8 November 2008
# The Author(s) 2008. This article is published with open access at Springerlink.com
Abstract The CCN family of matricellular proteins direct-
ly or indirectly affects development and differentiation. A
recent report written by Tan and colleagues (Am J Physiol
Cell Physiol 295: C740–C751 2008) shows that CCN2
inhibits adipocyte differentiation. This commentary sum-
marizes these observations.
Keywords CCN2 . Adipogenesis
Formation of new adipose tissue occurs in adult mammals
in response to excess energy supply. Adipocytes differen-
tiate from mesenchymal stem cells to adipocytes through a
series of well-characterized morphological and biological
changes, eventually accumulating lipid droplets (Fasshauer
et al. 2000). These m changes result from alterations of
expression and organization of the extracellular matrix and
cytoskeleton (Croissandeau et al. 2002).
Transforming growth factor β (TGF-β) inhibits adipo-
cyte differentition (Ignotz and Massague 1985), and is
found in increased levels in adipose tissue of both animal
and human models of obesity (Alessi et al. 2000). CCN2
(connective tissue growth factor, CTGF) is a downstream
mediator and/or co-regulator of the actions of TGF-β in
fibrosis (Leask and Abraham 2004). Although TGF-β1
inhibits adipocyte differentiation, whether CCN2 has a
similar role has not been reported.
In a recent study, the effect of CCN2 on adipogenesis
was assessed. NIH/3T3-L1 fibroblast cells were differenti-
ated into fat by standard methods, in the presence or
absence of CCN2 (Tan et al. 2008). The degree of
differentiation was measured by the expression of differen-
tiation markers as well as the accumulation of lipids, as
visualized by Oil Red O staining. CCN2 inhibited adipo-
nectin expression and lipid accumulation, and suppressed
the expression of the decreased lipogenic enzyme glycerol-
3-phosphate dehydrogenase. The CCAAT/enhancer binding
proteins (C/EBPs) are a family of transcription factors. Of
these, C/EBP-α and C/EBP-β being transiently increased at
the early phase of adipocyte differentiation; C/EBP-α is
required for the differentiation of preadipocytes to mature
adipocytes in most white adipose tissue depots (Lane et al.
1999). Tan and colleagues (2008) found that CCN2
suppressed C/EBP-α mRNA expression and nuclear local-
ization. Similar results were observed in CCN2-treated
primary adipocytes. Finally, CCN2 expression was ob-
served in central fat depots in vivo.
Collectively, these data suggest that CCN2 may influ-
ence the degree of adipocyte differentiation in vivo.
However, further experiments are required to clarify this
issue. Moreover, although the results presented suggest that
CCN2 may act by suppressing C/EBP-α, this hypothesis
has yet to be tested. In fact, the mechanism by which CCN2
acts to reduce adipogenesis needs to be thoroughly
investigated. In the future, it will be interesting to see
whether CCN2 suppresses obesity in vivo. Nonetheless, the
data presented in this novel work are an important first step,
and suggest the intriguing notion that CCN2 may ultimately
be used as a therapy for obesity.
J. Cell Commun. Signal. (2008) 2:93–94
DOI 10.1007/s12079-008-0032-4
A. Leask (*)
Division of Oral Biology and Department of Physiology
and Pharmacology, Schulich School of Medicine and Dentistry,
University of Western Ontario,
Dental Sciences Building,
London, ON N6A 5C1, Canada
e-mail: Andrew.Leask@schulich.uwo.ca
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
References
Alessi MC, Morange P, Juhan-Vague I (2000) Fat cell function and
fibrinolysis. Horm Metab Res 32:504–508
Croissandeau G, Chretien M, Mbikay M (2002) Involvement of
matrix metalloproteinases in the adipose conversion of 3T3-L1
preadipocytes. Biochem J 364:739–746 doi:10.1042/BJ20011158
Fasshauer M, Klein J, Ueki K, Kriauciunas KM, Benito M, White MF,
Kahn CR (2000) Essential role of insulin receptor substrate-2 in
insulin stimulation of Glut4 translocation and glucose uptake in
brown adipocytes. J Biol Chem 275:25494–25501 doi:10.1074/
jbc.M004046200
Ignotz RA, Massague J (1985) Type beta transforming growth
factor controls the adipogenic differentiation of 3T3 fibro-
blasts. Proc Natl Acad Sci USA 82:8530–8534 doi:10.1073/
pnas.82.24.8530
Lane MD, Tang QQ, Jiang MS (1999) Role of the CCAAT enhancer
binding proteins (C/EBPs) in adipocyte differentiation. Biochem
Biophys Res Commun 266:677–683 doi:10.1006/bbrc.1999.1885
Leask A, Abraham DJ (2004) TGF-β signaling and the fibrotic
response. FASEB J 18:816–827 doi:10.1096/fj.03-1273rev
Tan JTM, McLennan SV, Song WW, Lo LWY, Bonner JG, Williams
PF, Twigg SM (2008) Connective tissue growth factor inhibits
adipocyte differentiation. Am J Physiol Cell Physiol 295:740–
751 doi:10.1152/ajpcell.00333.2007
94 A. Leask


Fat cell function and fibrinolysis. Horm Metab Res 32:504–508 Croissandeau

file:///data/remote/core/dit/data/Springer-OA/pdf/446/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjEwMDcvczEyMDc5LTAwOC0wMDMyLTQucGRm.pdf

The skinny on CCN2

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Crossref

Springer - Publisher Connector