The absorption and disposition kinetics of the soy isoflavone genistein were determined in cats ( n = 6). An oral dose of 100 mg/kg was administered, which has previously been demonstrated to be the minimum oral estrogenic dose, and was administered intravenously at a dose of 20 mg/kg, being the largest practical dose that could be safely administered. Plasma free, and total (conjugated + free) genistein concentrations were determined by HPLC following organic extraction. Noncompartmental analysis revealed a half‐life of 21.67 ± 7.9 h (free) and 9.95 ± 2.7 h (conjugated), volume of distribution 31.94 ± 10.38 L/kg (free) and 11.82 ± 3.96 L/kg (conjugated) following intravenous administration. Following oral administration the half‐lives were determined to be 17 ± 4.8 h (free) and 8.56 ± 4.65 h (conjugated), with t max = 4.4 ± 0.6 h (free) and 4.42 ± 0.99 h (conjugated), and C max = 0.276 ± 0.1 μ g/mL (free) and 6.24 ± 6.58 μ g/mL (conjugated). Oral bioavailabilities were 1.379 ± 0.9% (free) and 29.85 ± 22.61% (conjugated). The ratio of total:free genistein ranged from 25.9 to 5.5. Poor oral absorption and efficient conjugation explain the low bioavailability of free genistein. Accumulation of genistein in peripheral lipophilic compartments may occur.

The prevalence of obesity in domestic cats is increasing worldwide, and is strongly associated with gonadectomy. We have previously demonstrated the effectiveness of oestradiol in reducing food intake in both male and female neutered cats. This experiment was designed to test the hypothesis that oestradiol or genistein would prevent the increase in food intake following gonadectomy of male and female cats, and would prevent an increase in body fat mass. Three groups of eight cats each were surgically neutered then treated daily with either 0.5 mu g oestradiol subcutaneously, 100 mg/kg genistein orally, or vehicle only. Effect of treatment on food intake, vaginal cytology and body weight were recorded, and body composition was assayed using the D2O isotopic dilution method. Neutering was followed by an increase in food intake, bodyweight and body fat mass in the control group, which were almost completely prevented by treatment with oestradiol (p < 0.001). Treatment with genistein had no effect on food intake or bodyweight increase, but was associated with a significant increase in lean body mass (p = 0.018), and significantly less body fat accumulation than the control group (p = 0.01). There were no significant differences in responses to treatment between sexes. These findings demonstrate the importance of gonadal oestrogen for the control of food intake in male and female cats, and suggest the provision of an oestrogenic compound could help prevent obesity following neutering. In addition, the findings of this study are consistent with observations in rodents of the efficacy of genistein in inhibiting adipogenesis and promoting lean body tissue development.

AIM: To determine if exogenous oestradiol or the phyto-oestrogen genistein could reduce food intake in male and female cats fed ad libitum that had been allowed to accrue excessive bodyfat following neutering.METHODS: Sixteen adult (eight female, eight male) cats were neutered and allowed to increase their bodyweight (BW) through feeding ad libitum of a complete and balanced dry diet. Oestradiol was injected subcutaneously for 5-day periods in incremental doses (0.25-4 mu g per cat), then food intake was recorded, and vaginal cytological changes were observed in females. Similarly, genistein was administered orally for 5-day periods in incremental doses (5-100 mg/kg).RESULTS: In males and females, both oestradiol (p < 0.001) and genistein (p= 0.037) significantly reduced food intake during treatment, and the minimum daily doses that produced a signifi cant effect were 0.5 mu g and 100 mg/kg, respectively. The minimum daily dose of oestradiol that produced a signifi cant effect on food intake was not associated with changes in vaginal cytology over the 5-day treatment period.CONCLUSIONS AND CLINICAL RELEVANCE: Gonadal oestradiol appeared to be a key modulator of food intake in both male and female cats, and replacement of oestrogen to neutered cats via oestradiol or an oestrogen surrogate such as genistein has potential for reducing the prevalence of obesity in neutered cats.