The role of the liver

(Andrea Bonetto 2021)

The liver, one of the largest organs in our body, is required to metabolize and detoxify xenobiotics, as well to complete important metabolic reactions. The liver is also an important secretory organ and plays a critical role in the acute phase response. 

Aside from musculoskeletal complications, occurrence of cancers such as colorectal cancer also causes perturbations to the liver, especially in its most advanced/metastatic stages. We and others have recently demonstrated that colorectal cancer triggers oxidative-to-glycolytic shifts in hepatic metabolism, along with increased gluconeogenesis and net negative energy balance, which are hallmarks of cachexia. However, whether liver abnormalities also partake in the progression of cancer cachexia by influencing bone and/or muscle homeostasis is largely unknown. Importantly, the liver also provides endocrine functions via secretion of liver-specific soluble factors (i.e., hepatokines), some of which are known to mediate musculoskeletal health via inter-tissue communication in disease states, (e.g., nonalcoholic fatty liver disease, type 2 diabetes) and aging. Yet, whether hepatokines are involved in the musculoskeletal wasting that occurs in cancer cachexia remains to be fully understood. Our recent work demonstrating that formation of colorectal liver metastases is accompanied by exacerbated skeletal muscle and bone loss would seem to implicate a direct role of the liver in musculoskeletal health in cachexia. 

Our group is actively involved in understanding the musculoskeletal complications resulting from abnormal hepatokine secretion in colorectal cancer to the extent of identifying novel cachexia treatments.