Phytoestrogens in my lab animal diet! Withdrawal of phytoestrogens in adult life induces obesity and alters hypothalamic food intake control

ANDREOLI MF; STOKER C; ROSSETTI MF; RAMOS JG

Workshop; IWNE 2015; 2015

Phytoestrogens are nonsteroidal compounds found in many legumes and are particularly abundant in soy products. In almost all commercially available rodent diets, soy is used as a main source of protein. As a consequence, experimental animals have been bred and maintained for many generations on soy-containing feed, thus driving selection for traits that allow them to tolerate the relatively high levels of phytoestrogens present in commonly used commercial feeds. This fact focused our interest on the effects of a commercial diet as a relevant model of phytoestrogen intake, rather than exposing animals to pure phytoestrogens. Phytoestrogens have the capacity to bind both ER  and  and to mimic estrogenic actions. Because both ERs are present in tissues responsible for the regulation of metabolism, the implication that phytoestrogens regulate metabolism appears plausible. Estrogens have been shown to influence body weight, food intake and adipose tissue deposition. Multiple studies have suggested that, similar to estrogens, dietary phytoestrogens play a beneficial role in reducing obesity and diabetes, and also removing phytoestrogens from rodent feed during pregnancy and lactation in CD-1 mice produces an obese phenotype in the litter and impairs glucose tolerance. On this basis, our lab focused on the effects of removing phytoestrogens from feed in the adulthood. Our study demonstrated for the first time that phytoestrogen withdrawal in the adult stage of life induces obesity in male rats. Energy intake was elevated involving an orexigenic hypothalamic response with reduced expression of anorectic neuropeptides and increased expression of orexigenic signals. Changing commercial animal chow by a low phytoestrogen diet modified endocrine homeostasis, reflecting a variety of physiological changes closely associated to obesity. One of the most remarkable alterations was the impairment of glucose homeostasis?a hallmark of insulin resistance and diabetes. Remarkably, the obese phenotype observed was more pronounced than in high fat fed animals, a model widely known to induce marked weight gain. The ubiquity of phytoestrogens in the diet of humans and laboratory animals emphasizes the necessity of further research in this field.