Cachexia, a metabolic disorder marked by uncontrolled weight loss and muscle wasting in chronic diseases and cancer, affects more than just skeletal muscles, according to a new study led by Helmholtz Munich. The research, conducted in collaboration with the Institute of Physiology of the Czech Academy of Sciences, Heidelberg University Hospital, the German Center for Diabetes Research (DZD), and the German Center for Cardiovascular Research (DZHK), shows that multiple organs respond in a coordinated manner, contributing to the devastating weight loss seen in cancer patients. The study is published in Nature Metabolism.
Cancer-associated cachexia impacts 50–80% of patients and significantly diminishes quality of life, reducing the effectiveness of cancer therapies and increasing mortality. Even modest weight loss—around 10% of body weight over six months—can cause serious health complications, leaving patients unable to maintain or regain weight despite adequate nutrition.
“Until now, it was completely unclear how the metabolic responses of different organs interact to drive cancer-related weight loss,” said Dr. Maria Rohm, co-corresponding author and group leader at Helmholtz Munich’s Institute for Diabetes and Cancer. Her team investigated the interplay between glucose and lipid metabolism across multiple organs to uncover potential therapeutic targets.
Using tumor-bearing mouse models, researchers conducted comprehensive metabolomic and transcriptomic analyses across eight organs, identifying a cachexia-specific metabolic and genetic signature. The study revealed that all organs exhibited hyperactivation of the “one carbon cycle,” a biochemical pathway critical for nucleotide and amino acid synthesis and cell regeneration. Metabolites such as sarcosine and dimethylglycine may serve as future biomarkers for cachexia.
The findings also linked overactive one carbon metabolism in muscles to glucose hypermetabolism and muscle atrophy. Comparative studies across eight tumor models—including lung, colon, and pancreatic cancers—confirmed that this metabolic signature is universal, independent of cancer type.
“It was surprising that all organs respond metabolically in the same way to cachexia,” Rohm said. “Individual metabolic signatures are lost, and the organs align with a coordinated systemic process.”
Currently, Germany has no approved treatments for cancer cachexia, and most therapeutic strategies focus on appetite loss. This study provides new evidence that targeting the one carbon cycle could normalize metabolism itself. Early cell culture experiments suggest interventions in this pathway may prevent muscle wasting.
Future research, including efforts by the DFG Research Group “HyperMet,” will explore whether systemic or organ-specific therapies are more effective. The ultimate goal is to stabilize metabolic processes, improve patient quality of life, and enhance the efficacy of cancer treatments.
