以色列魏茨曼科学研究所Elazar Zelzer研究团队，揭示了感觉神经元中的Piezo2调节全身和脂肪组织代谢。2025年2月6日出版的《细胞—代谢》发表了这项成果。

课题组表明，通过机械传感器Piezo2，感觉神经元调节棕色和米色脂肪的形态和生理特性，并防止全身高代谢状态。针对Runx3/parvalbumin（PV）感觉神经元的基因模型小鼠，表现出一种全身代谢表型，特征为体脂减少、胰岛素敏感性和葡萄糖耐受性增强。

PV感觉神经元中Piezo2的缺失再现了这种表型，防止高脂肪饮食引起的肥胖，并导致脂肪组织褐变和变黑，这可能是由去甲肾上腺素水平升高驱动的。发现棕色和米色脂肪是由表达Piezo2的Runx3/PV感觉神经元支配的，这为一个模型提供了证据——在感觉神经元中，Piezo2感知到的机械信号保护能量储存，并防止全身性高代谢表型的发生。

据了解，全身代谢通过器官间的相互作用，调节产热脂肪组织以确保能量稳态。与交感神经系统在诱导产热脂肪中的作用已被广泛描述不同，确保能量保存的抑制信号仍然不甚明确。

附：英文原文

Title: Piezo2 in sensory neurons regulates systemic and adipose tissue metabolism

Author: Fabian S. Passini, Bavat Bornstein, Sarah Rubin, Yael Kuperman, Sharon Krief, Evi Masschelein, Tevie Mehlman, Alexander Brandis, Yoseph Addadi, Shira Huri-Ohev Shalom, Erik A. Richter, Tal Yardeni, Amir Tirosh, Katrien De Bock, Elazar Zelzer

Issue&Volume: 2025-02-06

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 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.

DOI: 10.1016/j.cmet.2024.12.016

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00526-6