Fumagillin reduces adipose tissue formation in murine models of nutritionally induced obesity

Henri R Lijnen1, Liesbeth Frederix, Berthe Van Hoef

  • 1Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium. roger.lijnen@med.kuleuven.be

Insights

Fumagillin treatment reduced body weight and fat mass in diet-induced obese mice by decreasing adipocyte size. This obesity drug shows potential for managing metabolic disorders.

Area of Science:

  • Pharmacology
  • Metabolic Diseases
  • Obesity Research

Background:

  • Obesity is a complex metabolic disorder with significant health implications.
  • Diet-induced obesity models in mice are crucial for studying disease mechanisms and potential treatments.
  • Methionine aminopeptidase-2 (MetAP2) inhibitors, like fumagillin, have shown antiangiogenic properties.

Purpose of the Study:

  • To investigate the efficacy of fumagillin in mitigating diet-induced obesity in a murine model.
  • To assess the impact of fumagillin on body weight, fat mass, adipocyte size, and adipose tissue angiogenesis.

Main Methods:

  • Male C57Bl/6 mice were fed a high-fat diet (HFD) and treated with fumagillin (1 mg/kg/day) or a solvent control for 4 weeks.
  • Body weight, subcutaneous (SC) and gonadal (GON) fat mass were measured.
  • Adipocyte size, density, and normalized blood vessel density were analyzed in adipose tissues.
  • A separate cohort of obese mice received short-term fumagillin to assess effects on established obesity.

Main Results:

  • Fumagillin treatment significantly reduced body weight and SC/GON fat mass compared to controls (P < 0.0005, P < 0.005, P < 0.05).
  • Adipose tissues exhibited smaller adipocytes and higher adipocyte density in fumagillin-treated mice.
  • Normalized blood vessel density was lower in fumagillin-treated mice, but short-term administration in established obesity caused adipocyte hypotrophy without affecting blood vessel parameters.

Conclusions:

  • Fumagillin effectively impairs diet-induced obesity in mice.
  • The anti-obesity effect is associated with adipocyte hypotrophy.
  • Fumagillin does not appear to significantly impact adipose tissue angiogenesis in this context, despite its known antiangiogenic properties.

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