Metabolic, Inflammatory, and Molecular Impact of Cancer Cachexia on the Liver

Abstract

Cancer-associated cachexia (CAC) is a severe wasting syndrome, marked by involuntary weight loss and muscle wasting. It is a leading cause of cancer-related morbidity and mortality, and is driven by systemic, chronic low-grade inflammation. Key cytokines, such as IL-6 and GDF15, activate catabolic pathways in many organs. This study examined the role of inflammation and metabolic disruption in the liver during CAC, focusing on its dual role as both a target and a source of inflammatory factors. The analysis covered protein and lipid metabolism disturbances, including the hepatic production of acute-phase proteins and insulin resistance. Hepatic inflammation contributes to systemic dysfunction in CAC. The increased production of C-Reactive Protein (CRP) impacts muscle wasting, while liver inflammation leads to insulin resistance and hepatic steatosis, aggravating the cachectic state. Therefore, understanding the molecular mechanisms of liver metabolism in CAC is essential for developing effective therapies. Potential interventions include anti-inflammatory treatments, anabolic strategies, and restoration of lipid metabolism. Further research is necessary to explore the liver's full contribution to CAC and its systemic effects, allowing to the development of liver-targeted therapeutic strategies.

Keywords: cachexia; cancer; inflammation; liver; metabolism.

Figure 1

Schematic overview of the liver’s central role in the development of cachexia. The Liver interacts with the immune system, muscle tissue, and adipose tissue in cycles involving inflammation, proteolysis, and fat mobilization. The figure was created using resources from BioRender (https://www.biorender.com), accessed on 15 October 2024.