HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wheatcroft, S. B. Articles by Crossey, P. A. Search for Related Content PubMed PubMed Citation Articles by Wheatcroft, S. B. Articles by Crossey, P. A. Social Bookmarking                What's this?

IGF-Binding Protein-2 Protects Against the Development of Obesity and Insulin Resistance

¹ Diabetes and Cardiovascular Research in Leeds, The LIGHT Laboratories, University of Leeds, U.K
² Cardiovascular Division, King’s College London, U.K
³ Institute of Psychiatry, King’s College London, U.K
⁴ Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K
⁵ School of Biomedical and Molecular Sciences, University of Surrey, U.K

Address correspondence and reprint requests to Prof. Mark Kearney, Academic Unit of Cardiovascular Medicine, The LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT, U.K. E-mail: m.t.kearney{at}leeds.ac.uk

Abbreviations: BBSRC, Biotechnology and Biological Sciences Research Council; BHF, British Heart Foundation; GTT, glucose tolerance test; IBMX, isobutylmethylxanthine; IGFBP, IGF-binding protein; MRC, Medical Research Council; MRI, magnetic resonance imaging; PPAR, peroxisome proliferator–activated receptor

Proliferation of adipocyte precursors and their differentiation into mature adipocytes contributes to the development of obesity in mammals. IGF-I is a potent mitogen and important stimulus for adipocyte differentiation. The biological actions of IGFs are closely regulated by a family of IGF-binding proteins (IGFBPs), which exert predominantly inhibitory effects. IGFBP-2 is the principal binding protein secreted by differentiating white preadipocytes, suggesting a potential role in the development of obesity. We have generated transgenic mice overexpressing human IGFBP-2 under the control of its native promoter, and we show that overexpression of IGFBP-2 is associated with reduced susceptibility to obesity and improved insulin sensitivity. Whereas wild-type littermates developed glucose intolerance and increased blood pressure with aging, mice overexpressing IGFBP-2 were protected. Furthermore, when fed a high-fat/high-energy diet, IGFBP-2–overexpressing mice were resistant to the development of obesity and insulin resistance. This lean phenotype was associated with decreased leptin levels, increased glucose sensitivity, and lower blood pressure compared with wild-type animals consuming similar amounts of high-fat diet. Our in vitro data suggest a direct effect of IGFBP-2 preventing adipogenesis as indicated by the ability of recombinant IGFBP-2 to impair 3T3-L1 differentiation. These findings suggest an important, novel role for IGFBP-2 in obesity prevention.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. K. Sethi and A. J. Vidal-Puig Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation J. Lipid Res., June 1, 2007; 48(6): 1253 - 1262. [Abstract] [Full Text] [PDF]