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

Su, Hua and Gunter, Jennifer H. and de Vries, Melissa and Connor, Tim and Wanyonyi, Stephen and Newell, Felicity S. and Segal, David and Molero, Juan Carlos and Reizes, Ofer and Prins, Johannes B. and Hutley, Louise J. and Walder, Ken and Whitehead, Jonathan P. and UNSPECIFIED (2009) Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity. Biochemical and Biophysical Research Communications, 386 (2). pp. 351-355. ISSN 0006-291X

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Files associated with this item cannot be displayed due to copyright restrictions.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 18 Oct 2017 04:07
Last Modified: 18 Oct 2017 04:07
Uncontrolled Keywords: 3T3-L1 cells; Adipogenesis; drug effects; animals; diet
Fields of Research : 11 Medical and Health Sciences > 1116 Medical Physiology > 111601 Cell Physiology
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920106 Endocrine Organs and Diseases (excl. Diabetes)
Identification Number or DOI: 10.1016/j.bbrc.2009.06.040
URI: http://eprints.usq.edu.au/id/eprint/30697

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