Fumagillin Reduces Adipose Tissue Formation in Murine Models of Nutritionally Induced Obesity

• Published in: Obesity (Silver Spring, Md.) Md.), 2010-12, Vol.18 (12), p.2241-2246
• Main Authors: Lijnen, Henri R., Frederix, Liesbeth, Hoef, Berthe
• Format: Article
• Language: English
• Subjects: Adipose Tissue - blood supply; Adipose Tissue - cytology; Adipose Tissue - drug effects; Aminopeptidases - antagonists & inhibitors; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; Aspergillus fumigatus - chemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Body fat; Body Fat Distribution; Body Weight - drug effects; Cyclohexanes - pharmacology; Cyclohexanes - therapeutic use; Dietary Fats - adverse effects; Fatty Acids, Unsaturated - pharmacology; Fatty Acids, Unsaturated - therapeutic use; Glycoproteins - antagonists & inhibitors; Male; Mice; Mice, Inbred C57BL; Obesity - blood; Obesity - chemically induced; Obesity - drug therapy; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2009.503

The effect of fumagillin (a methionine aminopeptidase‐type 2 (Met‐AP2) inhibitor, with antiangiogenic properties) was investigated in murine models of diet‐induced obesity. Eleven‐week‐old male C57Bl/6 mice (group 1) were given fumagillin by oral gavage at a dose of 1 mg/kg/day during 4 weeks while fed a high‐fat diet (HFD) (20.1 kJ/g), and control mice (group 2) received solvent and were pair‐fed. At the end of the experiment, body weights in group 1 were significantly lower as compared to group 2 (P < 0.0005). The subcutaneous (SC) and gonadal (GON) fat mass was also significantly lower in group 1 (P < 0.005 and P < 0.05, respectively). Adipocytes were smaller in adipose tissues of mice in group 1, associated with higher adipocyte density. Blood vessel density normalized to adipocyte density was lower in group 1 adipose tissues. However, in mice with established obesity monitored to maintain the same body weight and fat mass as controls, short‐term fumagillin administration was also associated with adipocyte hypotrophy (P = 0.01) without affecting blood vessel size or density. Thus, treatment with fumagillin impaired diet‐induced obesity in mice, associated with adipocyte hypotrophy but without marked effect on adipose tissue angiogenesis.