Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity
Data(s) |
21/08/2009
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Resumo |
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.<br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
Academic Press |
Relação |
http://dro.deakin.edu.au/eserv/DU:30019917/molero-inhibitionof-2009.pdf http://dx.doi.org/10.1016/j.bbrc.2009.06.040 |
Direitos |
2009, Elsevier |
Palavras-Chave | #IMPDH #adipocyte #guanine nucleotides #obesity |
Tipo |
Journal Article |