UC San Diego

Estrogen is involved in many important reproductive and metabolic processes in mammals. Since evidence suggests that gut microbes may facilitate the protective effect of estrogen on metabolic dysregulation, we investigated whether the gut microbiome plays a role in the diet-independent weight gain that occurs after ovariectomy (OVX) in adult female mice. We found that OVX was not associated with changes in alpha diversity but was correlated with a shift in beta diversity of gut bacteria. Additionally, we observed differences in the relative abundance of a few bacterial taxa such as Turicibacter 3-5 weeks post-OVX. A complementary cohousing study was performed to determine whether exposure to a healthy gut microbiome was protective against development of the OVX-induced metabolic phenotype. We found that cohousing OVX mice with sham-operated mice did not improve OVX-induced metabolic phenotype. Altogether, these results indicate that post-OVX changes in the gut microbiome are unlikely to play a causal role in the weight gain observed after OVX. Due to the strong metabolic phenotype of a letrozole-induced (LET) polycystic ovary syndrome mouse (PCOS) model that we previously investigated, we compared the metabolic phenotypes of pubertal LET mice with pubertal OVX mice to determine which phenotypes may be mediated by low estrogen. We found that pubertal OVX mice and pubertal LET mice both had metabolic dysregulation including elevated weight gain, fasting blood glucose, fasting blood insulin, and parametrial fat. However, only LET mice developed insulin resistance, indicating that estradiol deficiency alone is not sufficient to induce insulin resistance in pubertal mice.