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Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity

Su, Hua, Gunter, Jennifer H., de Vries, Melissa, Connor, Tim, Wanyonyi, Stephen, Newell, Felicity S., Segal, David, Molero, Juan Carlos, Reizes, Ofer, Prins, Johannes B., Hutley, Louise J., Walder, Ken and Whitehead, Jonathan P. 2009, Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity, Biochemical and biophysical research communications, vol. 386, no. 2, pp. 351-355.

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Title Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity
Author(s) Su, Hua
Gunter, Jennifer H.
de Vries, Melissa
Connor, Tim
Wanyonyi, Stephen
Newell, Felicity S.
Segal, David
Molero, Juan Carlos
Reizes, Ofer
Prins, Johannes B.
Hutley, Louise J.
Walder, Ken
Whitehead, Jonathan P.
Journal name Biochemical and biophysical research communications
Volume number 386
Issue number 2
Start page 351
End page 355
Publisher Academic Press
Place of publication San Diego, Calif.
Publication date 2009-08-21
ISSN 0006-291X
1090-2104
Keyword(s) IMPDH
adipocyte
guanine nucleotides
obesity
Summary We previously described a putative role for inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, in lipid accumulation. Here we present data which demonstrate that IMPDH activity is required for differentiation of preadipocytes into mature, lipid-laden adipocytes and maintenance of adipose tissue mass. In 3T3-L1 preadipocytes inhibition of IMPDH with mycophenolic acid (MPA) reduced intracellular GTP levels by 60% (p < 0.05) and blocked adipogenesis (p < 0.05). Co-treatment with guanosine, a substrate in the salvage pathway of nucleotide biosynthesis, restored GTP levels and adipogenesis demonstrating the specificity of these effects. Treatment of diet-induced obese mice with mycophenolate mofetil (MMF), the prodrug of MPA, for 28 days did not affect food intake or lean body mass but reduced body fat content (by 36%, p = 0.002) and adipocyte size (p = 0.03) and number. These data suggest that inhibition of IMPDH may represent a novel strategy to reduce adipose tissue mass.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2009
Copyright notice ©2009, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019917

Document type: Journal Article
Collections: School of Medicine
Institute for Technology Research and Innovation
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Created: Fri, 25 Sep 2009, 09:41:19 EST by Sally Morrigan