PURPOSE: The aim of this study was to determine whether a Fraxinus excelsior L. seed extract, FraxiPure (0.5% in the diet), limits weight gain and hyperglycemia in mice. In a previous report, we identified several secoiridoids in FraxiPure, some of which activated peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro and inhibited the differentiation of 3T3-L1 preadipocyte cells. In a separate study, FraxiPure reduced glycemia in healthy volunteers, following an oral glucose tolerance test. These findings suggest that FraxiPure has antiobesity and antihyperglycemia effects. MATERIALS AND METHODS: FraxiPure was tested in mice that were fed a high-fat diet over 16 weeks and compared with low-fat and high-fat diet controls. Weight gain, omental and retroperitoneal fat, fasting blood glucose, and fasting blood insulin were measured. RESULTS: FraxiPure reduced gains in body weight by 32.30% (p < 0.05), omental fat by 17.92%, and retroperitoneal fat by 17.78%. FraxiPure also lowered fasting blood glucose levels by 76.52% (p < 0.001) and plasma insulin levels by 53.43% (p < 0.05) after 16 weeks. Moreover, FraxiPure lowered liver weight gains by 63.62% (p < 0.05) and the incidence of fatty livers by 66.67%. CONCLUSIONS: Our novel results demonstrate the antiobesity effects of chronic administration of an F. excelsior seed extract and confirm its ability to regulate glycemia and insulinemia. In addition, this extract, which is rich in secoiridoid glucosides, protects against obesity-related liver steatosis. CI - Copyright (c) 2010 Elsevier GmbH. All rights reserved.