Y2 receptor signalling in NPY neurons controls bone formation and fasting induced feeding but not spontaneous feeding

Area of Science:

• Neuroscience
• Endocrinology
• Obesity Research

Background:

• Y2 receptors are implicated in obesity and regulate feeding behaviors.
• The specific neurons mediating Y2 receptor functions in feeding are not fully understood.
• Neuropeptide Y (NPY) neurons are key regulators of appetite.

Purpose of the Study:

• To investigate the role of Y2 receptors specifically in NPY neurons.
• To determine the impact of Y2 receptor deletion in NPY neurons on feeding and energy balance.
• To explore the involvement of Y2 receptors in regulating NPY and POMC expression.

Main Methods:

• Utilized a novel inducible, postnatal onset NPY neuron-specific Y2 receptor deletion mouse model.
• Assessed spontaneous and fasting-induced food intake.
• Monitored body weight and body weight gain.
• Measured NPY and POMC mRNA expression in the arcuate nuclei (Arc).
• Evaluated bone mineral content.

Main Results:

• Y2 receptor deletion in NPY neurons did not affect spontaneous food intake.
• Fasting-induced food intake was increased in the first hour post-refeeding.
• Body weight gain was increased in male mice, but overall body weight changes were not significant.
• Y2 receptor signaling's role in suppressing bone formation was conserved, with decreased bone mineral content.
• NPY and POMC mRNA expression in the Arc was altered, confirming Y2 receptor's role.

Conclusions:

• Y2 receptors in NPY neurons critically regulate NPY and POMC expression in the Arc.
• Loss of Y2 receptors in NPY neurons impacts fasting-induced feeding but not spontaneous intake.
• These findings suggest that non-NPY neuronal Y2 receptors also play a significant role in regulating feeding and energy homeostasis.