๐ค Authors: Aliesha Garrett, Naama Darzi, Ashlesha Deshmukh, Nataly Rosenfeld, Omer Goldman, Lital Adler, Elizabeta Bab-Dinitz, Oded Singer, Alireza Hassani Najafabadi, Chi Wut Wong, Shree Bose, Peggy M Randon, Francisco Bustamante, Rene Larios, Alexander Brandis, Tevie Mehlman, Brandon Smaglo, Ping Chang, Jacqueline Oliva, Cara Haymaker, Laukik Nagawekar, Sophie R Wu, Yixuan Huang, Aidan Shen, Ahana Vora, Jon Floyd Padilla, Alissa Pfeffer, Gary Sutherland, Mark Starr, Teresa Zimmers, Yangzhi Zhu, James Morizio, Ayelet Erez, Xiling Shen
Vagal blockade of the brain-liver axis deters cancer-associated cachexia.
Cancer-associated cachexia (CAC) is a multifactorial and currently incurable syndrome responsible for nearly one-third of cancer-related deaths. It contributes to therapy resistance and increases mortality among affected patients.
In this study, we show that cancer-induced systemic inflammation alters vagal tone in CAC mouse models. This vagal dysregulation disrupts the brain-liver vagal axis, leading to a reprogramming of hepatic protein metabolism through the depletion of HNF4ฮฑ, a key transcriptional regulator of liver function.
The loss of HNF4ฮฑ disrupts hepatic metabolism and promotes systemic inflammation, resulting in cachectic phenotypes. Interventions targeting the right cervical vagus nerve surgically, chemically, electrically, or through a non-invasive transcutaneous device attenuate CAC progression, alleviate its clinical manifestations, and synergize with chemotherapy to improve overall health and survival in mice.
