My lab is interested in how the ovarian steroid hormones, estradiol and progesterone, regulate behavior and energy homeostasis. These hormones elicit many of their biological effects by binding to their respective intracellular steroid receptors located in target tissues throughout the body, including the brain. Our work has explored how nuclear receptor coactivators dramatically enhance the transcriptional activity of these steroid receptors in brain (Acharya et al., 2017).
Recently, we have been studying how estrogens regulate energy homeostasis. Estrogens have profound effects on energy homeostasis and weight gain in women and female rodents. For example, post-menopausal women have decreased levels of estrogens and tend to gain weight, which increases their risk of obesity, diabetes, heart disease and cancer. Estrogens have similar metabolic effects in female mice. We and others have shown that ovariectomized mice fed a high-fat diet become obese, while mice treated with estrogens remain lean (Bless et al., 2014). We’ve found that estrogens and diet can regulate neurogenesis in the female mouse hypothalamus, a brain region involved in feeding and energy homeostasis. Moreover, some of these newborn neurons can respond to estrogens and leptin, another hormone involved in energy metabolism (Bless et al., 2016).
We have extended these studies on energy homeostasis to include how estrogens influence the gut microbiome, which is a collection of microorganisms (bacteria, viruses, archaea, protozoa and fungi), their genomes and the factors they produce in the gut. The gut microbiome has been implicated in a variety of disorders and diseases, including obesity, diabetes, depression and anxiety (Tetel et al., 2018). In collaboration with Jason Kim (UMass Medical School), we are studying the effects of estrogens and diet on metabolism and gut microbiota in female mice. While the decline in estrogens during menopause causes weight gain, this decrease in estrogens is also associated with depression, anxiety, stress and sleep disturbances. In collaboration with Otsuka Pharmaceuticals, we are investigating the effects of estrogens and gut microbiota on anxiety in female mice. Finally, working with Marina Walther-Antonio and Nicholas Chia (Mayo Clinic) and Christen Deveney (Psychology), we are studying how diet, exercise and mood affect the human microbiome.
See the Team page for a more detailed description of each lab member’s ongoing project and to catch up with our lab alums.