Biozentrum, University of Basel, Basel 4056, Switzerland.
Biozentrum, University of Basel, Basel 4056, Switzerland.
Mol Metab. 2022 Nov;65:101580. doi: 10.1016/j.molmet.2022.101580. Epub 2022 Aug 23.
Adipose tissue, via sympathetic and possibly sensory neurons, communicates with the central nervous system (CNS) to mediate energy homeostasis. In contrast to the sympathetic nervous system, the morphology, role and regulation of the sensory nervous system in adipose tissue are poorly characterized.
Taking advantage of recent progress in whole-mount three-dimensional imaging, we identified a network of calcitonin gene-related protein (CGRP)-positive sensory neurons in murine white adipose tissue (WAT). We found that adipose mammalian target of rapamycin complex 2 (mTORC2), a major component of the insulin signaling pathway, is required for arborization of sensory neurons, but not of sympathetic neurons. Time course experiments revealed that adipose mTORC2 is required for maintenance of sensory neurons. Furthermore, loss of sensory innervation in WAT coincided with systemic insulin resistance. Finally, we established that neuronal protein growth-associated protein 43 (GAP43) is a marker for sensory neurons in adipose tissue.
Our findings indicate that adipose mTORC2 is necessary for sensory innervation in WAT. In addition, our results suggest that WAT may affect whole-body energy homeostasis via sensory neurons.
脂肪组织通过交感神经和可能的感觉神经元与中枢神经系统（CNS）进行通讯，以介导能量平衡。与交感神经系统不同，感觉神经系统在脂肪组织中的形态、作用和调节仍知之甚少。
利用全器官三维成像的最新进展，我们在鼠白色脂肪组织（WAT）中鉴定出降钙素基因相关肽（CGRP）阳性感觉神经元网络。我们发现脂肪组织哺乳动物雷帕霉素靶蛋白复合物 2（mTORC2），胰岛素信号通路的主要组成部分，是感觉神经元分支所必需的，但不是交感神经元所必需的。时程实验表明，脂肪组织 mTORC2 是维持感觉神经元所必需的。此外，WAT 中的感觉神经支配丧失与全身胰岛素抵抗同时发生。最后，我们确定神经元蛋白生长相关蛋白 43（GAP43）是脂肪组织中感觉神经元的标志物。
我们的研究结果表明，脂肪组织 mTORC2 是 WAT 感觉神经支配所必需的。此外，我们的结果表明，WAT 可能通过感觉神经元影响全身能量平衡。
