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

Article

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), pp. 351-355. https://doi.org/10.1016/j.bbrc.2009.06.040
Article Title

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

ERA Journal ID2147
Article CategoryArticle
AuthorsSu, Hua (Author), Gunter, Jennifer H. (Author), de Vries, Melissa (Author), Connor, Tim (Author), Wanyonyi, Stephen (Author), Newell, Felicity S. (Author), Segal, David (Author), Molero, Juan Carlos (Author), Reizes, Ofer (Author), Prins, Johannes B. (Author), Hutley, Louise J. (Author), Walder, Ken (Author) and Whitehead, Jonathan P. (Author)
Journal TitleBiochemical and Biophysical Research Communications
Journal Citation386 (2), pp. 351-355
Number of Pages5
Year2009
Place of PublicationUnited States
ISSN0006-291X
1090-2104
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bbrc.2009.06.040
Web Address (URL)https://www.ncbi.nlm.nih.gov/pubmed/19523919
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.

Keywords3T3-L1 cells; Adipogenesis; drug effects; animals; diet
ANZSRC Field of Research 2020320801. Cell physiology
321402. Clinical pharmacology and therapeutics
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Byline AffiliationsUniversity of Queensland
Deakin University
Cleveland Clinic, United States
Institution of OriginUniversity of Southern Queensland
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