Piezo2 in sensory neurons regulates systemic and adipose tissue metabolism.

Summary

Using multiple genetic mouse models, the authors show that mechanosensory Piezo2 in Runx3/PV sensory neurons constrains thermogenic adipose remodeling and systemic hypermetabolism. Piezo2 deletion protects against high-fat-diet obesity, improves insulin sensitivity, and induces browning/beiging, likely via increased norepinephrine.

Key Findings

• Targeting Runx3/PV sensory neurons yielded reduced adiposity with improved insulin sensitivity and glucose tolerance.
• Piezo2 deletion in PV sensory neurons protected against high-fat-diet-induced obesity and induced browning/beiging of adipose tissue.
• Findings support a model where Piezo2-sensed mechanical signals in sensory neurons restrain systemic hypermetabolism, potentially via elevated norepinephrine.

Clinical Implications

If conserved in humans, modulating Piezo2-mediated sensory signaling could complement anti-obesity and insulin-sensitizing strategies by tuning adipose tissue thermogenesis.

Limitations

• Preclinical mouse data without direct human validation.
• Mechanistic link between mechanosensation and norepinephrine dynamics requires further causal dissection.

Future Directions

Validate Piezo2-sensory neuron control of adipose thermogenesis in human tissues or models; explore pharmacologic or neuromodulatory approaches to modulate this axis safely.