Effect of fumagillin on adipocyte differentiation and adipogenesis

Background: Inhibition of angiogenesis may impair adipose tissue development. Methods: The effect of fumagillin (a methionine aminopeptidase-2 inhibitor) on adipocyte differentiation and de novo adipogenesis was investigated in murine model systems. Results: During in vitro differentiation of murine 3T3-F442A preadipocytes, administration of fumagillin (>= 1 mu M) resulted in reduced expression of methionine aminopeptidase-2, and in enhanced differentiation rate. In vivo, de novo development of adipose tissue following injection of preadipocytes in nude mice kept on high fat diet was somewhat, but not significantly (p = 0.06), reduced by administration of fumagillin (1 mg/kg/day during 4 weeks by oral gavage). This was not associated with effects on blood vessel size or density, whereas blood vessel density normalized to adipocyte density was enhanced upon fumagillin treatment. In vivo BrdU incorporation experiments did not reveal effects of fumagillin on cell proliferation in adipose tissues, and cellular apoptosis was also not affected. Treatment with fumagillin enhances in vitro differentiation of preadipocytes, but has only a minor effect on in vivo adipogenesis. General Significance: These studies on in vitro and in vivo preadipcoyte differentiation thus do not Support an anti-obesity effect of fumagillin as a result of effects on adipocyte differentiation. (c) 2009 Elsevier B.V. All rights reserved.