Xidan Liu, Shijin Li, Qionghua Cui, Bujing Guo, Wanqiu Ding, Jie Liu, Li Quan, Xiaochuan Li, Peng Xie, Li Jin, Ye Sheng, Wenxin Chen, Kai Wang, Fanxin Zeng, Yifu Qiu, Changlu Liu, Yan Zhang, Fengxiang Lv, Xinli Hu, Rui-Ping Xiao
Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate...
March 18, 2024: Nature metabolism