Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons.

Area of Science:

• Neuroendocrinology
• Metabolic Neuroscience
• Hypothalamic Neuroscience

Background:

• Brain regulation of glucose homeostasis exhibits sexual dimorphism.
• The ventromedial hypothalamic nucleus (VMN) is a key brain region for metabolic sensing.
• Glucose-excited (GE) and glucose-inhibited (GI) neurons in the VMN are critical for energy balance.

Purpose of the Study:

• To investigate the sex-specific regulation of glucose-sensing neurons in the ventrolateral VMN (VL-VMN) by 17β-estradiol (17βE).
• To test the hypothesis that VL-VMN glucose-sensing neurons are sexually dimorphic and modulated by 17βE.

Main Methods:

• Electrophysiological recordings were performed on VL-VMN glucose-sensing neurons from male and female mice.
• Recordings were conducted in brain slices with and without the presence of 17βE.

Main Results:

• A novel class of adapting GI (AdGI) neurons in the VL-VMN was identified, showing transient responses to low glucose.
• Male nonadapting GI neurons exhibited a more robust low-glucose response than female counterparts; AdGI neurons did not show this dimorphism.
• 17βE blunted the low-glucose response of both nonadapting and AdGI neurons in both sexes, mediated by estrogen receptor β and AMP-activated kinase inhibition.
• 17βE did not affect GE or non-glucose sensing neurons.

Conclusions:

• Sexual dimorphism exists in VL-VMN glucose-sensing neurons.
• Estrogenic regulation of these neurons, particularly GI neurons, contributes to sex differences in glucose homeostasis.