Importantly, we detected the browning-associated markers UCP1 and PGC1α in a cachexia progression model and demonstrated that WAT atrophy by browning is an important and early manifestation of ESCC-induced cachexia development that occurs before skeletal muscle loss, consistent with previous observations in pancreatic adenocarcinoma.15 These studies, together with observations in LLC models (Supplementary Fig. 2), suggest that the involvement of WAT browning in the initiation and development of cachexia may not be limited to ESCC. This evidence concerns the gene PPARGC1A and esophageal squamous cell carcinoma.