Fumagillin reduces adipose tissue formation in murine models of nutritionally induced obesity.
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.
Lijnen
Henri R
HR
Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium. roger.lijnen@med.kuleuven.be
Frederix
Liesbeth
L
Van Hoef
Berthe
B
D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000737:chemistry*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D050218:Body Fat Distribution; D001835:Body Weight / Q000187:drug effects*; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D004041:Dietary Fats / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D008297:Male; D063208:Methionyl Aminopeptidases; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D019440:Anti-Obesity Agents; D001688:Biological Products; D003510:Cyclohexanes; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D006023:Glycoproteins; D012717:Sesquiterpenes; C026211:fumagillin; D000626:Aminopeptidases; C489894:Metap2 protein, mouse; D063208:Methionyl Aminopeptidases