Piezo2 in sensory neurons influences systemic and adipose tissue metabolism

Abstract

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 inhibit thermogenesis and prevent systemic hypermetabolism. Targeting Runx3/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 increased thermogenic fat activity, likely driven by elevated norepinephrine levels. Finding that thermogenic fat is innervated by Runx3/PV sensory neurons expressing Piezo2, suggests a model where mechanical signals sensed by Piezo2 in sensory neurons protect energy storages and inhibit adipose thermogenesis.

Competing Interest Statement

The authors have declared no competing interest.