Project: Regulation of Feeding Circuits by Hormones and Neuropeptides and Menopause

Model: Ovariectomized mice and Wild-type mice

Reproduction and feeding are closely tied and are under the tight control of the hypothalamic-pituitary axis. Menopause, a process that usually occurs with age, there is a precipitous decline in circulating estrogen levels, tends to be associated with an increased risk of obesity and health risks that leads to increased insulin resistance, dyslipidemia, high blood pressure, diabetes, heart disease and hypertension. Estrogen, a hormone secreted by the ovaries and leptin an hormone secreted by the fat cells is the main focus of this study. Our hypothesis is that estrogen and estrogen receptor (ER) signaling pathways play an important role in the regulation offeeding and energy expenditure by interaction with hypothalamic neural pathways. The objective of our proposal is to define the role that estrogen, ER and neuropeptide signaling play in the hypothalamus to influence energy homeostasis during menopause using follicle-depleted and ovariectomized mice (OVX) as model systems.

 

 

Experimental Questions

  1. How are the neuropeptide phenotypes (e.g. NPY/AGRP, POMC) of neurons in specific regions of the hypothalamus that are ER positive, both in normal and estrogen-deficient female mice regulated?
  2. Determine whether the neuropeptides (e.g. NPY/AGRP, POMC) colocalize with ER and the effect of estrogen-deficiency on their gene expression in the ARH and whether estrogen treatment alters the expression and circuits in any way?