Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity
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,...
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Veröffentlicht in: | Biochemical and biophysical research communications 2009-08, Vol.386 (2), p.351-355 |
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Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2009.06.040 |