Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat

Abstract

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow.

Fig. 1

Effect of isoflavone presence and hormone treatment on body weight in the OVX rat. On day 0, animals were either continued on standard chow diet or introduced to an IF diet. On day 13, animals received either VEH or E2 for the remainder of the study (14 days). On day 27 tissue was collected. IF chow fed animals had increased body weight compared to standard chow fed animals (at day 13 and day 27). E2 treatment prevented post-OVX weight gain in both diet conditions (at day 27). Data points represent average body weight values ± SEM of n = 10 animals per treatment group; * p < 0.05.

Fig. 2

The presence of isoflavone and hormone treatment on food and water consumption at days 13 and 27. a Amount of food consumed on day 13 (prior to E2 treatment). Animals fed an IF diet had decreased food consumption compared to animals fed standard chow. b Amount of food consumed at day 27 (after E2 treatment). E2 replacement decreased food consumption in IF diet animals. The combination of E2 treatment and IF chow resulted in decreased food consumption compared to E2 treated animals fed standard chow. c Amount of water consumed at day 13. There is no difference in water consumption regardless of food condition. d Amount of water consumed on day 27. There was no difference regardless of food or hormone treatment. Bars represent mean values ± SEM. At day 13, n = 10 per treatment group. At day 27, n = 5 per treatment group; * p < 0.05).

Fig. 3

Effect of dietary isoflavones and hormone treatment on abdominal fat weight and uterine weight in the OVX rat. a Animals exposed to isoflavones in standard chow had decreased abdominal fat weight compared to animals fed an IF diet. In the standard chow condition, E2 treatment decreased abdominal fat weight. b As expected, animals treated with E2 had increased uterine weights compared to animals treated with VEH. All samples were collected at day 27. Bars represent mean values ± SEM of n = 10 animals; * p < 0.05).

Fig. 4

Circulating adipokines as a result of food condition and E2 treatment in the OVX rat. a Animals fed standard chow had an increased levels of circulating leptin compared to animals fed an IF diet. E2 replacement decreased the amount of serum leptin within each food condition. b IF diet alone (VEH) resulted in increased GRO/KC expression compared to standard chow. E2 treatment resulted in decreased serum GRO/KC in animals fed IF chow. c In animals fed an IF diet, E2 replacement decreased serum RANTES expression. d After E2 administration, IF chow fed animals had decreased IL-10 expression compared to standard chow fed animals. e Serum IL-18 levels were decreased in E2 treated, IF chow fed animals compared to E2 treated, standard chow fed animals. Within the IF chow fed condition, animals receiving E2 replacement had decreased IL-18 compared to animals receiving VEH. f E2 treatment decreased serum expression of MCP-1 within each food condition compared to VEH. Samples were collected on day 27. Bars represent mean ± SEM of n = 6–10 animals per treatment group; * p < 0.05).