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, 386 2: 351-355. doi:10.1016/j.bbrc.2009.06.040


Author 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.
Title Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 2009-08-21
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2009.06.040
Open Access Status
Volume 386
Issue 2
Start page 351
End page 355
Total pages 5
Editor W. Baumeister
Place of publication New York
Publisher Academic Press
Language eng
Subject 0601 Biochemistry and Cell Biology
C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920106 Endocrine Organs and Diseases (excl. Diabetes)
060104 Cell Metabolism
110104 Medical Biochemistry: Lipids
110306 Endocrinology
Abstract 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.
Keyword IMPDH
Mitotic Clonal Expansion
Adipocyte
Guanine nucleotides
Obesity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Thu, 03 Sep 2009, 17:51:39 EST by Mr Andrew Martlew on behalf of UQ Diamantina Institute