A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation.

Compared with the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work has revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. PIEZO2 deletion in fat-innervating neurons induced transcriptional programs in adipose tissue resembling sympathetic activation, mirroring DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.