The brain detects alterations in energy balance and glucose levels through autonomic and neuroendocrine controls. Hypothalamic neuroendocrine circuits coordinating growth hormone (GH) secretion operate within complex physiological settings, regulating proper responses to various stressors. We are utilizing unique mouse models to analyze a novel population of hypothalamic neurons that are critical for the feedback inhibition of GH production, in controlling systemic glucose homeostasis and regulate aging processes.
Using designer receptors exclusively activated by designed drugs (DREADDs; expressed as DREADD-mCherry fusion proteins) technique to control the GHR+neuronal activity, we demonstrated that activation of GHG expressing neurons in the hypothalamus promotes whole-body glucose utilization and significantly improves glucose tolerance. Furthermore, using state-of-the-art techniques to determine in vivo insulin sensitivity (hyperinsulinemic-euglycemic clamp), we have identified GHR-expressing neuronal population in the hypothalamic arcuate nucleus (ARC) as a major regulator of glycolysis and muscle insulin sensitivity.
We are currently exploring molecular mechanisms in the hypothalamus that trigger an age-associated shift in energy homeostasis induced by the GH axis, which underlie the metabolic imbalance in aging.