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Publication : Piezo2 in sensory neurons regulates systemic and adipose tissue metabolism.

First Author  Passini FS Year  2025
Journal  Cell Metab Volume  37
Issue  4 Pages  987-1000.e6
PubMed ID  39919739 Mgi Jnum  J:363380
Mgi Id  MGI:7869167 Doi  10.1016/j.cmet.2024.12.016
Citation  Passini FS, et al. (2025) Piezo2 in sensory neurons regulates systemic and adipose tissue metabolism. Cell Metab
abstractText  Systemic metabolism ensures energy homeostasis through inter-organ crosstalk regulating thermogenic adipose tissue. Unlike the well-described inductive role of the sympathetic system, the inhibitory signal ensuring energy preservation remains poorly understood. Here, we show that, via the mechanosensor Piezo2, sensory neurons regulate morphological and physiological properties of brown and beige fat and prevent systemic hypermetabolism. Targeting runt-related transcription factor 3 (Runx3)/parvalbumin (PV) sensory neurons in independent genetic mouse models resulted in a systemic metabolic phenotype characterized by reduced body fat and increased insulin sensitivity and glucose tolerance. Deletion of Piezo2 in PV sensory neurons reproduced the phenotype, protected against high-fat-diet-induced obesity, and caused adipose tissue browning and beiging, likely driven by elevated norepinephrine levels. Finding that brown and beige fat are innervated by Runx3/PV sensory neurons expressing Piezo2 suggests a model in which mechanical signals, sensed by Piezo2 in sensory neurons, protect energy storage and prevent a systemic hypermetabolic phenotype.
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