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经皮耳迷走神经刺激通过调节肥胖大鼠的支链氨基酸代谢促进脂肪组织褐变和线粒体完整性:一项实验研究。

Transcutaneous auricular vagus nerve stimulation promotes adipose tissue browning and mitochondrial integrity by regulating BCAA metabolism in obese rats: an experimental study.

作者信息

Xin Chen, Li Shaoyuan, Feng Bowen, Sun Lan, Wang Yifei, Zhang Jinling, Zhang Yuzhengheng, Zou Ningyi, Zhou Qing, Rong Peijing

机构信息

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Int J Surg. 2025 Jul 1;111(7):4866-4871. doi: 10.1097/JS9.0000000000002451. Epub 2025 May 16.

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) may exert its anti-obesity effects by promoting the browning of adipose tissue with unclear mechanisms. Modulation of branched-chain amino acid (BCAA) metabolism in adipose tissue may play a key role in this process. In this study, 6 weeks of taVNS significantly reduced body weight gain, body mass index, and the accumulation of inguinal and epididymal white adipose tissue in high-fat diet-induced obese rats, with effects comparable to those of orlistat. Notably, taVNS increased both the content and thermogenic activity of interscapular brown adipose tissue (BAT) in obese rats. Infrared thermal imaging confirmed increased BAT thermogenesis, while transmission electron microscopy indicated improved mitochondrial morphology and function. Molecular analysis revealed that taVNS upregulated uncoupling protein 1, the transporter protein solute carrier family 25 member 44 (SLC25A44), and protein phosphatase Mg2+/Mn2+ dependent 1 K (PPM1K) expression while downregulating branched-chain α-ketoacid dehydrogenase kinase, thereby promoting BCAA metabolism and adipose tissue browning. We conclude that the anti-obesity effects of taVNS are closely related to BCAA metabolism in BAT. These findings highlight taVNS as a promising approach for obesity management, though further studies are needed to clarify the neurobiological pathways involved and advance taVNS technology.

摘要

经皮耳迷走神经刺激(taVNS)可能通过促进脂肪组织褐变发挥其抗肥胖作用,但其机制尚不清楚。脂肪组织中支链氨基酸(BCAA)代谢的调节可能在此过程中起关键作用。在本研究中,6周的taVNS显著降低了高脂饮食诱导的肥胖大鼠的体重增加、体重指数以及腹股沟和附睾白色脂肪组织的积累,其效果与奥利司他相当。值得注意的是,taVNS增加了肥胖大鼠肩胛间棕色脂肪组织(BAT)的含量和产热活性。红外热成像证实BAT产热增加,而透射电子显微镜显示线粒体形态和功能得到改善。分子分析表明,taVNS上调了解偶联蛋白1、转运蛋白溶质载体家族25成员44(SLC25A44)和蛋白磷酸酶Mg2+/Mn2+依赖性1 K(PPM1K)的表达,同时下调了支链α-酮酸脱氢酶激酶,从而促进了BCAA代谢和脂肪组织褐变。我们得出结论,taVNS的抗肥胖作用与BAT中的BCAA代谢密切相关。这些发现突出了taVNS作为一种有前景的肥胖管理方法,尽管需要进一步研究来阐明所涉及的神经生物学途径并推进taVNS技术。

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