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, doi: 10.1016/j.bbrc.2009.06.040. Attached Files Name Description MIMEType Size Downloads 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 orcid.org/0000-0002-6758-4763 Whitehead, Jonathan P. Journal name Biochemical and biophysical research communications Volume number 386 Issue number 2 Start page 351 End page 355 Total pages 5 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 DOI 10.1016/j.bbrc.2009.06.040 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: Faculty of Health School of Medicine Institute for Technology Research and Innovation GTP Research Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Fri, 25 Sep 2009, 09:41:20 EST Mon, 28 Sep 2009, 09:07:07 EST Mon, 28 Sep 2009, 11:10:31 EST Mon, 28 Sep 2009, 11:11:25 EST Mon, 28 Sep 2009, 14:32:39 EST Tue, 20 Oct 2009, 11:30:14 EST Tue, 08 Dec 2009, 15:20:51 EST Wed, 09 Dec 2009, 11:06:45 EST Wed, 09 Dec 2009, 15:04:39 EST Fri, 02 Jul 2010, 13:59:25 EST Wed, 11 Aug 2010, 13:36:21 EST Thu, 12 Aug 2010, 11:56:51 EST Mon, 26 Nov 2012, 11:13:58 EST Mon, 26 Nov 2012, 11:15:26 EST Mon, 16 Jun 2014, 13:10:30 EST Wed, 02 Jul 2014, 17:01:34 EST Wed, 27 Aug 2014, 22:04:45 EST Filtered Full Citation counts:   Cited 6 times in TR Web of Science Cited 7 times in Scopus Search Google Scholar Access Statistics: 1037 Abstract Views, 1 File Downloads  -  Detailed Statistics Created: Fri, 25 Sep 2009, 09:41:19 EST by Sally Morrigan