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

Affiliations

¹ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
² Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁴ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA; The Phil & Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
⁵ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: liye@scripps.edu.
⁷ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: ardem@scripps.edu.

PMID: 40054462
DOI: 10.1016/j.cmet.2025.02.004

Free article

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

Yu Wang et al. Cell Metab. 2025.

Free article

. 2025 Apr 1;37(4):1001-1011.e7.

doi: 10.1016/j.cmet.2025.02.004. Epub 2025 Mar 6.

Authors

Affiliations

¹ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
² Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁴ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA; The Phil & Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
⁵ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: liye@scripps.edu.
⁷ Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: ardem@scripps.edu.

PMID: 40054462
DOI: 10.1016/j.cmet.2025.02.004

Abstract

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.

Keywords: adipose; mechanosensation.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation.
Wang Y, Zhang Y, Leung V, Seradj SH, Sonmez U, Servin-Vences R, Lipomi D, Ye L, Patapoutian A. Wang Y, et al. bioRxiv [Preprint]. 2024 Nov 19:2024.11.18.624210. doi: 10.1101/2024.11.18.624210. bioRxiv. 2024. Update in: Cell Metab. 2025 Apr 01;37(4):1001-1011.e7. doi: 10.1016/j.cmet.2025.02.004. PMID: 39605632 Free PMC article. Updated. Preprint.

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

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

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