Mechanism of Soy Isoflavone Daidzein-Induced Female-Specific Anorectic Effect

Abstract

Epidemiological studies suggest that regular intake of soy isoflavone exerts a preventive effect on postmenopausal obesity and other forms of dysmetabolism. Estrogens inhibit eating behavior. Soy isoflavones may act as estrogen agonist in estrogen-depleted conditions, whereas they may either act as an estrogen antagonist or be ineffective in estrogen-repleted conditions. We investigated the effects of dietary soy isoflavone on food intake under various estrogen conditions using male, ovariectomized (OVX), and non-OVX female rats, and compared the effects with those of estradiol. We found that soy isoflavones reduced food intake in females specifically, regardless of whether ovariectomy had been performed, whereas subcutaneous implantation of estradiol pellet did not reduce food intake in intact female rats, but did so in OVX female and male rats. Contrary to this hypothesis, the reduction in food intake may not be caused by the estrogenic properties of soy isoflavones. It is of great interest to understand the mechanisms underlying the anorectic effects of soy isoflavones. In this non-systematic review, we summarize our recent studies that have investigated the bioactive substances of anorectic action, pharmacokinetic properties of soy isoflavones, and the modification of central and peripheral signals regulating appetite by soy isoflavones, and selected studies that were identified via database mining.

Keywords: appetite; daidzein; equol; gastric emptying; hypothalamus.

Figure 1

Weekly changes in food intake in male (A), female (B), and ovariectomized rats (C) fed on a diet containing isoflavone aglycone-rich fermented soybean extract (containing 300 mg isoflavones/kg diet, closed circle) or the control diet without (open circle) or with (open triangle) subcutaneous implantation of estradiol pellet (4.2 μg/rat/day) for 4 weeks [23]. Each value represents the mean ± standard error. Asterisks show significant difference relative to rats fed on the control diet without subcutaneous implantation of estradiol pellet, determined using three-way ANOVA with repeated measures, followed by Student’s t-test with Bonferroni corrections. *, p < 0.05.

Figure 2

Diagram of the distribution of daidzein and equol in the body (A). Daily changes in daidzein and equol concentrations in bile (B) and serum (C) in intact female rats fed a diet containing 150 mg/kg daidzein [42]. Each value represents the mean ± standard error. Asterisks show significant difference relative to day 1, determined by Dunnett’s multiple comparison test. *, p < 0.05; ***, p < 0.001.

Figure 3

Diagram of a hypothesis regarding the mechanisms of the anorectic effect of daidzein (A). Changes in expression of neuropeptide-Y (Npy, (B)), galanin (Gal, (C)), and corticotrophin releasing hormone (Crh, (D)) mRNA in the rat hypothalamus, and cholecystokinin (Cck, (E)) mRNA in the rat upper small intestine before and after each meal [48]. Each value represents the mean ± standard error. Asterisks show a significant difference compared to the corresponding control group, and number signs show a significant difference compared to the corresponding before-meal group, determined by three-way ANOVA with Bonferroni corrections. * and #, p < 0.05.

Figure 4

Diagram for feeding schedules (A). Food intake during the first and second meals (B), and the amount of gastric emptying (C) in daily two meal-fed ovariectomized rats. Daily changes in food intake in ovariectomized rats with and without sleeve gastrectomy (D) [67]. Each value represents the mean ± standard error. Asterisks show significant difference relative to the control group, determined by an unpaired Student’s t-test. *, p < 0.05; **, p < 0.01. non-SG, intact groups; SG, sleeve gastrectomy-operated groups.