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

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.