Liver Plays a Key Role in Cancer-Related Weight Loss Through Systemic Signaling

Recent research has uncovered a significant role of the liver in the development of cancer cachexia, a syndrome marked by severe muscle and fat wasting often observed in cancer patients. Affecting approximately 50% of individuals with cancer, cachexia contributes to poor treatment outcomes, increased complications, and higher mortality rates.

A collaborative effort by scientists from Helmholtz Munich, Heidelberg University Hospital, the Technical University of Munich, and the German Center for Diabetes Research has identified the liver as an active participant in this wasting process. The study highlights how the liver responds systemically to tumors located in organs like the pancreas or intestine by releasing specific signaling molecules, which further exacerbate tissue degradation.

Central to this discovery is the silencing of the liver's internal clock gene, REV-ERBα, which normally regulates liver function throughout the day. When this gene is inactive, the liver produces increased levels of certain signaling proteins called hepatokines, notably LBP, ITIH3, and IGFBP1. These factors promote catabolic processes in muscle and fat tissues, leading to their breakdown. Elevated levels of these hepatokines have been found in the blood of patients with different types of cancer experiencing cachexia. Preclinical models demonstrate that targeting these molecules can reduce their harmful effects.

Further research revealed that reactivating REV-ERBα in the liver of affected mice significantly lessened weight loss, suggesting a potential therapeutic target. This advances understanding of cachexia as an active process driven by systemic organ interactions rather than purely passive cachexia resulting from tumor burden.

Dr. Mauricio Berriel Diaz, who led the study, emphasized the significance of these findings, stating that they open new pathways for the diagnosis and treatment of cachexia. The data resources generated from the study provide a comprehensive view of liver involvement in cachexia, which could lead to the development of biomarkers and novel therapies. Currently, there are no approved treatments for cachexia, underscoring the urgent need for new intervention strategies.

This research underscores the importance of considering systemic organ interactions in cancer progression and highlights the liver's active role in metabolic regulation and disease exacerbation.

Source: https://medicalxpress.com/news/2025-07-liver-cancer-cachexia-response.html